Nora volkow

As the toll of opioid-overdose deaths in the United States rises, we face an urgent need for prevention. But preventing such deaths will require a better understanding of the diverse trajectories by which overdoses occur, including the distinction between intentional (suicide) and unintentional..

Addiction, the most severe form of substance use disorder, is a chronic brain disorder molded by strong biosocial factors that has devastating consequences to individuals and to society. Our understanding of substance use disorder has advanced significantly over the last 3 decades in part due to major progress in genetics and neuroscience research and to the development of new technologies, including tools to interrogate molecular changes in specific neuronal populations in animal models of substance use disorder, as well as brain imaging devices to assess brain function and neurochemistry in humans...

The central adenosine system and adenosine receptors play a fundamental role in the modulation of dopaminergic neurotransmission. This is mostly achieved by the strategic co-localization of different adenosine and dopamine receptor subtypes in the two populations of striatal efferent neurons, striatonigral and striatopallidal, that give rise to the direct and indirect striatal efferent pathways, respectively. With optogenetic techniques it has been possible to dissect a differential role of the direct and indirect pathways in mediating "Go" responses upon exposure to reward-related stimuli and "NoGo" responses upon exposure to non-rewarded or aversive-related stimuli, respectively, which depends on their different connecting output structures and their differential expression of dopamine and adenosine receptor subtypes...

The origin of the "resting-state" brain activity recorded with functional magnetic resonance imaging (fMRI) is still uncertain. Here we provide evidence for the neurovascular origins of the amplitude of the low-frequency fluctuations (ALFF) and the local functional connectivity density (lFCD) by comparing them with task-induced blood-oxygen level dependent (BOLD) responses, which are considered a proxy for neuronal activation. Using fMRI data for 2 different tasks (Relational and Social) collected by the Human Connectome Project in 426 healthy adults, we show that ALFF and lFCD have linear associations with the BOLD response...

The FDA's "abstinence" outcome measure for approval of new medications to treat opioid-use disorders has been difficult to achieve; developing and validating alternative meaningful outcomes could facilitate drug development.

Cannabis is the most commonly used substance of abuse in the United States after alcohol and tobacco. With a recent increase in the rates of cannabis use disorder (CUD) and a decrease in the perceived risk of cannabis use, it is imperative to assess the addictive potential of cannabis. Here we evaluate cannabis use through the neurobiological model of addiction proposed by Koob and Volkow. The model proposes that repeated substance abuse drives neurobiological changes in the brain that can be separated into three distinct stages, each of which perpetuates the cycle of addiction...

BACKGROUND: The control of food intake in environments with easy access to highly rewarding foods is challenging to most modern societies. The combination of sustained release (SR) naltrexone and SR bupropion (NB32) has been used in weight-loss and obesity management. However, the effects of NB32 on the brain circuits implicated in the regulation of food intake are unknown. Here we used functional connectivity density (FCD) mapping to evaluate the effects of NB32 on resting brain FC. METHODS: Thirty-six healthy women underwent magnetic resonance imaging (MRI) before and after 4-week treatment with NB32 (n = 16) or with placebo (n = 20)...

Cocaine addiction is associated with dysfunction of the prefrontal cortex (PFC), which facilitates relapse and compulsive drug taking. To assess if cocaine's effects on both neuronal and vascular activity contribute to PFC dysfunction, we used optical coherence tomography and multi-wavelength laser speckle to measure vascularization and hemodynamics and used GCaMP6f to monitor intracellular Ca2+ levels ([Ca2+ ]in ) as a marker of neuronal activity. Rats were given short (1 hour; ShA) or long (6 hours; LgA) access cocaine self-administration...

Dopaminergic medications improve the motor symptoms of Parkinson's disease (PD), but their effect on response inhibition, a critical executive function, remains unclear. Previous studies primarily enrolled patients in more advanced stages of PD, when dopaminergic medication loses efficacy, and patients were typically on multiple medications. Here, we recruited 21 patients in early-stage PD on levodopa monotherapy and 37 age-matched controls to perform the stop-signal task during functional magnetic resonance imaging...

BACKGROUND: Cannabis abuse (CA) has been associated with psychopathology, including negative emotionality and higher risk of psychosis, particularly with early age of initiation. However, the mechanisms underlying this association are poorly understood. Because aberrant dopamine signaling is implicated in cannabis-associated psychopathology, we hypothesized that regular CA would be associated with altered resting-state functional connectivity in dopamine midbrain-striatal circuits. METHODS: We examined resting-state brain activity of subcortical regions in 441 young adults from the Human Connectome Project, including 30 subjects with CA meeting DSM-IV criteria for dependence and 30 control subjects matched on age, sex, education, body mass index, anxiety, depression, and alcohol and tobacco usage...

BACKGROUND: The primary goal of this study was to determine whether administration of intrathecal morphine reduces postoperative pain. The secondary goal was to determine the effect of intrathecal morphine upon circulating levels of the weakly analgesic endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and the related lipids palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). METHODS: Forty two total knee arthroplasty (TKA) patients were enrolled in a prospective, double-blinded, randomized study...

No abstract text is available yet for this article.

Neuroimaging studies have revealed brain functional abnormalities in frontal-mesolimbic regions in obesity. However, the effects of obesity on brain network topology remains largely unknown. In the current study, we employed resting-state functional magnetic resonance imaging and graph theory methods to investigate obesity-related changes in brain network topology in 26 obese patients and 28 normal weight subjects. Results revealed that the whole-brain networks of the two groups exhibited typical features of small-world topology...

It is hypothesized that brain network abnormalities in autism spectrum disorder (ASD) reflect local overconnectivity and long-range underconnectivity. However, this is not a consistent finding in recent studies, which could reflect the developmental nature and the heterogeneity of ASD. Here, we tested 565 ASD and 602 neurotypical (NT) males, and 91 ASD and 233 NT females using local functional connectivity density (lFCD) mapping and seed-voxel correlation analyses to assess how local and long-range connectivities differ in ASD...

No abstract text is available yet for this article.

Negative urgency (NU) and positive urgency (PU) are implicated in several high-risk behaviors, such as eating disorders, substance use disorders, and nonsuicidal self-injury behavior. The current study aimed to explore the possible link between trait of urgency and brain activity at rest. We assessed the amplitude of low-frequency fluctuations (ALFF) of the resting-state functional magnetic resonance imaging (fMRI) signal in 85 healthy volunteers. Trait urgency measures were related to ALFF in the lateral orbitofrontal cortex, dorsolateral prefrontal cortex, ventral and dorsal medial frontal cortex, anterior cingulate, and posterior cingulate cortex/precuneus...

BACKGROUND: Alcohol use disorder is underdiagnosed and undertreated, and up to 50% of alcohol-abstinent patients diagnosed with alcohol dependence relapse within the first year of treatment. Current treatments for the maintenance of alcohol abstinence in patients with alcohol use disorder have limited efficacy, and there is an urgent need for novel treatment strategies. Decreased cerebral glucose metabolism and increased brain uptake of acetate were recently reported in heavy drinkers, relative to controls...

No abstract text is available yet for this article.

Behaviours such as eating, copulating, defending oneself or taking addictive drugs begin with a motivation to initiate the behaviour. Both this motivational drive and the behaviours that follow are influenced by past and present experience with the reinforcing stimuli (such as drugs or energy-rich foods) that increase the likelihood and/or strength of the behavioural response (such as drug taking or overeating). At a cellular and circuit level, motivational drive is dependent on the concentration of extrasynaptic dopamine present in specific brain areas such as the striatum...

No abstract text is available yet for this article.