Addiction
addiction
The basal ganglia and addiction
Currents of Hope: how noninvasive brain stimulation is reshaping modern psychiatric care; Adapting to diversity: Integrating variability in brain structure and function into personalized / closed-loop non-invasive brain stimulation for substance use disorders
In March we will focus on TMS and host Ghazaleh Soleimani and Colleen Hanlon. The talks will talk place on Thursday, March 28th at noon ET – please be aware that this means 5PM CET since Boston already switched to summer time! Ghazaleh Soleimani, PhD, is a postdoctoral fellow in Dr Hamed Ekhtiari’s lab at the University of Minnesota. She is also the executive director of the International Network of tES/TMS for Addiction Medicine (INTAM). She will discuss “Adapting to diversity: Integrating variability in brain structure and function into personalized / closed-loop non-invasive brain stimulation for substance use disorders”. Colleen Hanlon, PhD, currently serves as a Vice President of Medical Affairs for BrainsWay, a company specializing in medical devices for mental health, including TMS. Colleen previously worked at the Medical University of South Carolina and Wake Forest School of Medicine. She received the International Brain Stimulation Early Career Award in 2023. She will discuss “Currents of Hope: how noninvasive brain stimulation is reshaping modern psychiatric care”. As always, we will also get a glimpse at the “Person behind the science”. Please register va talks.stimulatingbrains.org to receive the (free) Zoom link, subscribe to our newsletter, or follow us on Twitter/X for further updates!
Neuromodulation of subjective experience
Many psychoactive substances are used with the aim of altering experience, e.g. as analgesics, antidepressants or antipsychotics. These drugs act on specific receptor systems in the brain, including the opioid, serotonergic and dopaminergic systems. In this talk, I will summarise human drug studies targeting opioid receptors and their role for human experience, with focus on the experience of pain, stress, mood, and social connection. Opioids are only indicated for analgesia, due to their potential to cause addiction. When these regulations occurred, other known effects were relegated to side effects. This may be the cause of the prevalent myth that opioids are the most potent painkillers, despite evidence from head-to-head trials, Cochrane reviews and network meta-analyses that opioids are not superior to non-opioid analgesics in the treatment of acute or chronic non-cancer pain. However, due to the variability and diversity of opioid effects across contexts and experiences, some people under some circumstances may indeed benefit from prolonged treatment. I will present data on individual differences in opioid effects due to participant sex and stress induction. Understanding the effects of these commonly used medications on other aspects of the human experience is important to ensure correct use and to prevent unnecessary pain and addiction risk.
Targeting Maladaptive Emotional Memories to Treat Mental Health Disorders: Insights from Rodent Models
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.
Basal Ganglia in addiction
Integrative Neuromodulation: from biomarker identification to optimizing neuromodulation
Why do we make decisions impulsively blinded in an emotionally rash moment? Or caught in the same repetitive suboptimal loop, avoiding fears or rushing headlong towards illusory rewards? These cognitive constructs underlying self-control and compulsive behaviours and their influence by emotion or incentives are relevant dimensionally across healthy individuals and hijacked across disorders of addiction, compulsivity and mood. My lab focuses on identifying theory-driven modifiable biomarkers focusing on these cognitive constructs with the ultimate goal to optimize and develop novel means of neuromodulation. Here I will provide a few examples of my group’s recent work to illustrate this approach. I describe a series of recent studies on intracranial physiology and acute stimulation focusing on risk taking and emotional processing. This talk highlights the subthalamic nucleus, a common target for deep brain stimulation for Parkinson’s disease and obsessive-compulsive disorder. I further describe recent translational work in non-invasive neuromodulation. Together these examples illustrate the approach of the lab highlighting modifiable biomarkers and optimizing neuromodulation.
How can we treat visceral pain?
Chronic pain is a leading cause of morbidity, common to patients with gastrointestinal diseases such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Most pain killers are largely ineffective against this type of pain or restricted for use in these patients due to gut related complications and risk of addition. A significant unmet clinical need therefore exists to develop novel non-opioid based visceral analgesics.
ISAM-NIG Webinars
Optimized Non-Invasive Brain Stimulation for Addiction Treatment
Sex Differences in Learning from Exploration
Sex-based modulation of cognitive processes could set the stage for individual differences in vulnerability to neuropsychiatric disorders. While value-based decision making processes in particular have been proposed to be influenced by sex differences, the overall correct performance in decision making tasks often show variable or minimal differences across sexes. Computational tools allow us to uncover latent variables that define different decision making approaches, even in animals with similar correct performance. Here, we quantify sex differences in mice in the latent variables underlying behavior in a classic value-based decision making task: a restless two-armed bandit. While male and female mice had similar accuracy, they achieved this performance via different patterns of exploration. Male mice tended to make more exploratory choices overall, largely because they appeared to get ‘stuck’ in exploration once they had started. Female mice tended to explore less but learned more quickly during exploration. Together, these results suggest that sex exerts stronger influences on decision making during periods of learning and exploration than during stable choices. Exploration during decision making is altered in people diagnosed with addictions, depression, and neurodevelopmental disabilities, pinpointing the neural mechanisms of exploration as a highly translational avenue for conferring sex-modulated vulnerability to neuropsychiatric diagnoses.
Cell type-specific gene regulatory mechanisms associated with addiction-related behaviors in rats
Understanding the fundamental gene regulatory mechanisms underlying addiction and related behaviors could facilitate more effective treatments. We discuss our work using multi-omics methods to provide mechanistic and functional insights into how addiction perturbs gene regulatory programs in the rat brain, with single-cell resolution.
Brain and behavioural impacts of early life adversity
Abuse, neglect, and other forms of uncontrollable stress during childhood and early adolescence can lead to adverse outcomes later in life, including especially perturbations in the regulation of mood and emotional states, and specifically anxiety disorders and depression. However, stress experiences vary from one individual to the next, meaning that causal relationships and mechanistic accounts are often difficult to establish in humans. This interdisciplinary talk considers the value of research in experimental animals where stressor experiences can be tightly controlled and detailed investigations of molecular, cellular, and circuit-level mechanisms can be carried out. The talk will focus on the widely used repeated maternal separation procedure in rats where rat offspring are repeatedly separated from maternal care during early postnatal life. This early life stress has remarkably persistent effects on behaviour with a general recognition that maternally-deprived animals are susceptible to depressive-like phenotypes. The validity of this conclusion will be critically appraised with convergent insights from a recent longitudinal study in maternally separated rats involving translational brain imaging, transcriptomics, and behavioural assessment.
Neuromodulation of sleep integrity
The arousal construct underlies a spectrum of behaviors that include sleep, exploration, feeding, sexual activity and adaptive stress. Pathological arousal conditions include stress, anxiety disorders, and addiction. The dynamics between arousal state transitions are modulated by norepinephrine neurons in the locus coeruleus, histaminergic neurons in the hypothalamus, dopaminergic neurons in the mesencephalon and cholinergic neurons in the basal forebrain. The hypocretin/orexin system in the lateral hypothalamus I will also present a new mechanism underlying sleep fragmentation during aging. Hcrt neurons are hyperexcitable in aged mice. We identify a potassium conductance known as the M-current, as a critical player in maintaining excitability of Hcrt neurons. Genetic disruption of KCNQ channels in Hcrt neurons of young animals results in sleep fragmentation. In contrast, treatment of aged animals with a KCNQ channel opener restores sleep/wake architecture. These data point to multiple circuits modulating sleep integrity across lifespan.
The neuroscience of lifestyle interventions for mental health: the BrainPark approach
Our everyday behaviours, such as physical activity, sleep, diet, meditation, and social connections, have a potent impact on our mental health and the health of our brain. BrainPark is working to harness this power by developing lifestyle-based interventions for mental health and investigating how they do and don’t change the brain, and for whom they are most effective. In this webinar, Dr Rebecca Segrave and Dr Chao Suo will discuss BrainPark’s approach to developing lifestyle-based interventions to help people get better control of compulsive behaviours, and the multi-modality neuroimaging approaches they take to investigating outcomes. The webinar will explore two current BrainPark trials: 1. Conquering Compulsions - investigating the capacity of physical exercise and meditation to alter reward processing and help people get better control of a wide range of unhelpful habits, from drinking to eating to cleaning. 2. The Brain Exercise Addiction Trial (BEAT) - an NHMRC funded investigation into the capacity of physical exercise to reverse the brain harms caused by long-term heavy cannabis use. Dr Rebecca Segrave is Deputy Director and Head of Interventions Research at BrainPark, the David Winston Turner Senior Research Fellow within the Turner Institute for Brain and Mental Health, and an AHRPA registered Clinical Neuropsychologist. Dr Chao Suo is Head of Technology and Neuroimaging at BrainPark and a Research Fellow within the Turner Institute for Brain and Mental Health.
Stress deceleration theory: chronic adolescent stress exposure results in decelerated neurobehavioral maturation
Normative development in adolescence indicates that the prefrontal cortex is still under development thereby unable to exert efficient top-down inhibitory control on subcortical regions such as the basolateral amygdala and the nucleus accumbens. This imbalance in the developmental trajectory between cortical and subcortical regions is implicated in expression of the prototypical impulsive, compulsive, reward seeking and risk-taking adolescent behavior. Here we demonstrate that a chronic mild unpredictable stress procedure during adolescence in male Wistar rats arrests the normal behavioral maturation such that they continue to express adolescent-like impulsive, hyperactive, and compulsive behaviors into late adulthood. This arrest in behavioral maturation is associated with the hypoexcitability of prelimbic cortex (PLC) pyramidal neurons and reduced PLC-mediated synaptic glutamatergic control of BLA and nucleus accumbens core (NAcC) neurons that lasts late into adulthood. At the same time stress exposure in adolescence results in the hyperexcitability of the BLA pyramidal neurons sending stronger glutamatergic projections to the NAcC. Chemogenetic reversal of the PLC hypoexcitability decreased compulsivity and improved the expression of goal-directed behavior in rats exposed to stress during adolescence, suggesting a causal role for PLC hypoexcitability in this stress-induced arrested behavioral development. (https://www.biorxiv.org/content/10.1101/2021.11.21.469381v1.abstract)
Determinants of the transition to compulsion in addiction
Linking valence and anxiety in a mouse insula-amygdala circuit
Promising Neuroimmune Targets for Alcohol Use Disorder Pathology
Nr4a1 and chromatin bivalency in cocaine pathophysiology
Sex Differences in Addiction: lessons from animal models
Transcriptional and Epigenetic Mechanisms of Addiction
The mu opioid receptor and addiction
The Social Brain: From Models to Mental Health
Given the complex and dynamic nature of our social relationships, the human brain needs to quickly learn and adapt to new social situations. The breakdown of any of these computations could lead to social deficits, as observed in many psychiatric disorders. In this talk, I will present our recent neurocomputational and intracranial work that attempts to model both 1) how humans dynamically adapt beliefs about other people and 2) how individuals can exert influence over social others through model-based forward thinking. Lastly, I will present our findings of how impaired social computations might manifest in different disorders such as addiction, delusion, and autism. Taken together, these findings reveal the dynamic and proactive nature of human interactions as well as the clinical significance of these high-order social processes.
In-Love with Addiction Neuroscience
In this talk series, addiction neuroscientists from across the world share their personal stories/experiences on the beauty of addiction neuroscience and how/why they have decided to invest their scientific life in this field. We hope that this talk series would encourage and support a new generation of young and passionate addiction neuroscientists in different countries to revolutionize the field of addiction medicine.
How do I know my rat is addicted?
D1 and D2 Accumbens Neurons May not be Who You Think They Are: Distinct tetrapartite synaptic plasticity regulating drug relapse
Neuroimmune and Glutamatergic Mechanisms of Nicotine Addiction
In-Love with Addiction Neuroscience
In this talk series, addiction neuroscientists from across the world share their personal stories/experiences on the beauty of addiction neuroscience and how/why they have decided to invest their scientific life in this field. We hope that this talk series would encourage and support a new generation of young and passionate addiction neuroscientists in different countries to revolutionize the field of addiction medicine.
Habenular synaptic strength and neuronal dynamics for approach-avoidance behaviours
Acetylcholine dynamics in the basolateral amygdala during reward learning
Ready, Set, Go! Neural circuits underlying cognitive control of behavior
Mitochondrial mechanisms in psychostimulant and opioid action
In-Love with Addiction Neuroscience
In this talk series, addiction neuroscientists from across the world share their personal stories/experiences on the beauty of addiction neuroscience and how/why they have decided to invest their scientific life in this field. We hope that this talk series would encourage and support a new generation of young and passionate addiction neuroscientists in different countries to revolutionize the field of addiction medicine.
Dopamine release in the nucleus accumbens core signals perceived saliency
Addiction to cocaine: How you take the drug is more important than how much
Addiction: the compulsive pursuit of a behaviour, not only the drug
New genetically encoded sensors to track addiction-relevant neuromodulators in vivo
Striatal mechanisms underlying vulnerability for punishment-resistant alcohol drinking
In-Love with Addiction Neuroscience
In this talk series, addiction neuroscientists from across the world share their personal stories/experiences on the beauty of addiction neuroscience and how/why they have decided to invest their scientific life in this field. We hope that this talk series would encourage and support a new generation of young and passionate addiction neuroscientists in different countries to revolutionize the field of addiction medicine.
Pharmacokinetics trumps pharmacodynamics during drug reward valuation
Dopamine and relapse to drug seeking
Keeping the balance: a role for the insular cortex in emotion homeostasis
Non-canonical ventral pallidal circuits and their relevance for treating addiction
In-Love with Addiction Neuroscience
In this talk series, addiction neuroscientists from across the world share their personal stories/experiences on the beauty of addiction neuroscience and how/why they have decided to invest their scientific life in this field. We hope that this talk series would encourage and support a new generation of young and passionate addiction neuroscientists in different countries to revolutionize the field of addiction medicine.
The anterior insular cortex in the rat exerts an inhibitory influence over the loss of control of heroin intake and subsequent propensity to relapse
The anterior insular cortex (AIC) has been implicated in addictive behaviour, including the loss of control over drug intake, craving and the propensity to relapse. Evidence suggests that the influence of the AIC on drug-related behaviours is complex as in rats exposed to extended access to cocaine self-administration, the AIC was shown to exert a state-dependent, bidirectional influence on the development and expression of loss of control over drug intake, facilitating the latter but impairing the former. However, it is unclear whether this influence of the AIC is confined to stimulant drugs that have marked peripheral sympathomimetic and anxiogenic effects or whether it extends to other addictive drugs, such as opiates, that lack overt acute aversive peripheral effects. We investigated in outbred rats the effects of bilateral excitotoxic lesions of AIC induced both prior to or after long-term exposure to extended access heroin self-administration, on the development and maintenance of escalated heroin intake and the subsequent vulnerability to relapse following abstinence. Compared to sham surgeries, pre-exposure AIC lesions had no effect on the development of loss of control over heroin intake, but lesions made after a history of escalated heroin intake potentiated escalation and also enhanced responding at relapse. These data show that the AIC inhibits or limits the loss of control over heroin intake and propensity to relapse, in marked contrast to its influence on the loss of control over cocaine intake.
In-Love with Addiction Neuroscience
In this talk series, addiction neuroscientists from across the world share their personal stories/experiences on the beauty of addiction neuroscience and how/why they have decided to invest their scientific life in this field. We hope that this talk series would encourage and support a new generation of young and passionate addiction neuroscientists in different countries to revolutionize the field of addiction medicine.
A multiscale approach to brain disorders
Schizophrenia and Substance Use Disorders: Cracking the Chicken-or-Egg Question
Although substance use disorders (SUDs) occur commonly in patients with schizophrenia and significantly worsen their clinical course, the neurobiological basis of SUDs in schizophrenia is not well understood. Therefore, there is a critical need to understand the mechanisms underlying SUDs in schizophrenia in order to identify potential targets for therapeutic intervention. Since drug use usually begins in adolescence, it is also important to understand the long-term effects of adolescent drug exposure on schizophrenia- and reward- related behaviors and circuitry. This talk will combine pharmacological, behavioral, electrophysiologic (local field potential recordings) and pre-clinical magnetic resonance imaging (resting-state functional connectivity and magnetic resonance spectroscopy) approaches to study these topics with an eye toward developing better treatment approaches.
In-Love with Addiction Neuroscience
In this talk series, addiction neuroscientists from across the world share their personal stories/experiences on the beauty of addiction neuroscience and how/why they have decided to invest their scientific life in this field. We hope that this talk series would encourage and support a new generation of young and passionate addiction neuroscientists in different countries to revolutionize the field of addiction medicine.
Neuronal encoding of drug choices and preference in the orbitofrontal cortex
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).
Social deprivation, coping and drugs: a bad cocktail in the COVID-19 era: evidence from preclinical studies
The factors that underlie an individual’s vulnerability to switch from controlled, recreational drug use to addiction are not well understood. I will discuss the evidence in rats that in individuals housed in enriched conditions, the experience of drugs in the relative social and sensory impoverishment of the drug taking context, and the associated change in behavioural traits of resilience to addiction, exacerbate the vulnerability to develop compulsive drug intake. I will further discuss the importance of the acquisition of alcohol drinking as a mechanism to cope with distress as a factor of exacerbated vulnerability to develop compulsive alcohol intake. Together these results demonstrate that experiential factors in the drug taking context, which can be substantially driven by social isolation, shape the vulnerability to addiction.
In-Love with Addiction Neuroscience
In this talk series, addiction neuroscientists from across the world share their personal stories/experiences on the beauty of addiction neuroscience and how/why they have decided to invest their scientific life in this field. We hope that this talk series would encourage and support a new generation of young and passionate addiction neuroscientists in different countries to revolutionize the field of addiction medicine.
Biomarkers for Addiction Treatment Development: fMRI Drug Cue Reactivity as an Example
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)
In-Love with Addiction Neuroscience
In this talk series, addiction neuroscientists from across the world share their personal stories/experiences on the beauty of addiction neuroscience and how/why they have decided to invest their scientific life in this field. We hope that this talk series would encourage and support a new generation of young and passionate addiction neuroscientists in different countries to revolutionize the field of addiction medicine.
The role of spatiotemporal waves in coordinating regional dopamine decision signals
The neurotransmitter dopamine is essential for normal reward learning and motivational arousal processes. Indeed these core functions are implicated in the major neurological and psychiatric dopamine disorders such as schizophrenia, substance abuse disorders/addiction and Parkinson's disease. Over the years, we have made significant strides in understanding the dopamine system across multiple levels of description, and I will focus on our recent advances in the computational description, and brain circuit mechanisms that facilitate the dual role of dopamine in learning and performance. I will specifically describe our recent work with imaging the activity of dopamine axons and measurements of dopamine release in mice performing various behavioural tasks. We discovered wave-like spatiotemporal activity of dopamine in the striatal region, and I will argue that this pattern of activation supports a critical computational operation; spatiotemporal credit assignment to regional striatal subexperts. Our findings provide a mechanistic description for vectorizing reward prediction error signals relayed by dopamine.
Neuroimaging in human drug addiction: an eye towards intervention development
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.
Astrocytic control of dopamine contributes to addiction and reward
FENS Forum 2024
Compulsive-like seeking behavior correlates with AMPA receptor rectification in synapses of the subthalamic nucleus in a rat model of cocaine addiction
FENS Forum 2024
Deconstruction of the role of CB1 receptor in CaMKII+ neurons in the context of obesity, metabolic syndrome, binge-eating, and food addiction
FENS Forum 2024
Effects of 5-HT2AR-mGluR2-based interventions on electrophysiological biomarkers in a rat model of alcohol addiction
FENS Forum 2024
Epigenetic mechanisms of information storage in the onset of drug addiction
FENS Forum 2024
Examination of adolescent cannabinoid vapour exposure effects on behavioural predictors of addiction and alcohol use disorder features in adult male and female rats
FENS Forum 2024
Identifying the biological relationship among the stages and patterns of cocaine addiction and behaviors that predict drug abuse
FENS Forum 2024
The mechanism underlying acupuncture inhibition of addiction behaviors through activation of mesolimbic GABA neurons
FENS Forum 2024
Prefrontal-hippocampal neural dynamics underlying impulsive-like behavior in food addiction
FENS Forum 2024
Prenatal hypoxia, maternal stress, and the impact on CHRNA7 gene expression: Linking to nicotine addiction in adult offspring
FENS Forum 2024
Role of the interneurons in prefrontal-based attentional dysfunctions in nicotine addiction
FENS Forum 2024
Shared genetics between addiction, aggression, and related behavioural traits
FENS Forum 2024
Social context and drug cues modulate inhibitory control in cocaine addiction: Involvement of the STN evidenced through functional MRI
FENS Forum 2024