Nora D Volkow

National Institutes of Health | NIH · National Institute of Drug Abuse (NIDA)

Previous fMRI studies have showed obesity-related alterations in intrinsic functional connectivity (FC) within and between different resting-state networks (RSNs). However, few studies have examined dynamic functional connectivity (DFC). Thus, we employed resting-state fMRI with independent component analysis (ICA) and DFC analysis to investigate a...

Despite bariatric surgery being the most effective treatment for obesity, a proportion of subjects have suboptimal weight loss post-surgery. Therefore, it is necessary to understand the mechanisms behind the variance in weight loss and identify specific baseline biomarkers to predict optimal weight loss. Here, we employed functional magnetic resona...

Obese individuals exhibit brain functional abnormalities in multiple regions implicated in reward/motivation, emotion/memory, homeostatic regulation and executive-control when exposed to food-cues and during rest. However, it remains unclear whether abnormal brain responses to food-cues might account for or relate to their abnormal activity in rest...

The biological mediators that support cognitive-control and long-term weight-loss after laparoscopic sleeve gastrectomy (LSG) remain unclear. We measured peripheral appetitive hormones and brain functional-connectivity (FC) using magnetic-resonance-imaging with food cue-reactivity task in 25 obese participants at pre, 1-month and 6-month after LSG,...

Objective Obese individuals have shown functional abnormalities in frontal-limbic regions, and bariatric surgery is an effective treatment for morbid obesity. The aim of the study was to investigate how bariatric surgery modulates brain regional activation and functional connectivity (FC) to food cues, and whether the underlying structural connecti...

Obese subjects show enhanced brain responses in motivation and reward neurocircuitry encompassing sensory and somatic integration-interception, motivation–reward (striatal), emotion, and memory processes, which attenuate frontal region activation during food cues. Bariatric surgery (BS) is the only reliable treatment for morbid obesity. Unfortunate...

Objective Obese individuals have shown functional abnormalities in frontal-limbic regions, and bariatric surgery is an effective treatment for morbid obesity. The aim of the study was to investigate how bariatric surgery modulates brain regional activation and functional connectivity (FC) to food cues, and whether the underlying structural connecti...

Objective: To investigate alterations in functional-connectivity (FC) within and interactions between between resting-state- networks (RSNs) involved in salience, executive-control and interoception in subjects with obesity (OB). Methods: Using RS-fMRI with independent component analysis and FC, we investigated alterations within and interactions...

Cannabis use increased among pregnant women in the United States from 2002 to 2014. However, changes in cannabis use and frequency by trimester over time and national prevalence of medical cannabis use during pregnancy are unknown. Data from the National Survey on Drug Use and Health (NSDUH) were examined to address these knowledge gaps.

Background/Objective: Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric surgery to treat obesity, and involves removal of the gastric fundus where ghrelin is mainly produced. Ghrelin stimulates appetite and regulates food-intake through its effect on the hypothalamus and hippocampus (HIPP). While ghrelin’s role on the hypothalamus has...

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...

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...

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...

Obese individuals exhibit brain alterations of resting-state functional connectivity (RSFC) integrity of resting-state networks (RSNs) related to food intake. Bariatric surgery is currently the most effective treatment for combating morbid obesity. How bariatric surgery influences neurocircuitry is mostly unknown. Functional connectivity density (F...

Obesity-related brain gray (GM) and white matter (WM) abnormalities have been reported in regions associated with food-intake control and cognitive-emotional regulation. Bariatric surgery (BS) is the most effective way to treat obesity and induce structural recovery of GM/WM density and WM integrity. It is unknown whether the surgery can promote st...

Obesity-related brain gray (GM) and white matter (WM) abnormalities have been reported in regions associated with food-intake control and cognitive-emotional regulation. Bariatric surgery (BS) is the most effective way to treat obesity and induce structural recovery of GM/WM density and WM integrity. It is unknown whether the surgery can promote st...

Extraordinary focus by all segments of society is required to respond to the nation’s opioid crisis. Now is the time to channel the efforts of the scientific community to deliver effective—and sustainable—solutions to this formidable public health challenge. Recognizing this opportunity, Congress added $500 million to the base appropriation of the...

Neuroinflammation appears to contribute to neurotoxicity observed with heavy alcohol consumption. To assess whether chronic alcohol results in neuroinflammation we used PET and [11C]PBR28, a ligand that binds to the 18-kDa translocator protein (TSPO), to compare participants with an alcohol use disorder (AUD: n = 19) with healthy controls (HC: n =...

Physical activity (PA) is associated with various aspects of physical and mental health and varies by age and BMI. We aimed to compare PA measures obtained with wrist and ankle accelerometers and characterize their associations with age and BMI. We assessed PA mean and PA variability (indexed by coefficient of variation (CV)) at daytime and nightti...

Physical activity and demographics raw data. Excel file containing acceleration raw data in 0.1 g units (m/s^2) for 47 participants included in all analyses. Column A indicates subject number. Columns B-E contain mean and CV data of ankle at daytime and nighttime. Columns F-I contain wrist mean and CV data for daytime and nighttime. Columns J-M con...

Significance There has been an emerging interest in sleep and its association with β-amyloid burden as a risk factor for Alzheimer’s disease. Despite the evidence that acute sleep deprivation elevates β-amyloid levels in mouse interstitial fluid and in human cerebrospinal fluid, not much is known about the impact of sleep deprivation on β-amyloid b...

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...

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 d...

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 hemodynamic...

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 pa...

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,...

Subcortical Local Functional Hyperconnectivity in Cannabis Dependence Biological Psychiatry: Cognitive Neuroscience and Neuroimaging In Press, Corrected Proof

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...

Background: Alcohol use disorder is under-diagnosed and under-treated, 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 no...

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...

Background Cannabis abuse has been associated with psychopathology, including negative emotionality and a higher risk of psychosis, particularly with early age of initiation. However, the mechanisms underlying this association are poorly understood. Because aberrant dopamine (DA) signaling is implicated in cannabis-associated psychopathology, we hy...

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 (ALF...

Adolescence is a time of dramatic changes in brain structure and function, and the adolescent brain is highly susceptible to being altered by experiences like substance use. However, there is much we have yet to learn about how these experiences influence brain development, how they promote or interfere with later health outcomes, or even what heal...

To assess how tobacco smoking status affects baseline dopamine D2/D3 (D2R) receptor availability and methylphenidate-induced dopamine (DA) release, we retrospectively analyzed D2R availability measures of 8 current smokers, 10 ex-smokers, and 18 non-smokers who were scanned with Positron Emission Tomography and [(11)C]raclopride, after administrati...

Appetitive drive is influenced by coordinated interactions between brain circuits that regulate reinforcement and homeostatic signals that control metabolism. Glucose modulates striatal dopamine (DA), and regulates appetitive drive and reinforcement learning. Striatal DA D2 receptors (D2R) also regulate reinforcement learning, and are implicated in...

It remains unclear whether resting state functional magnetic resonance imaging (rfMRI) networks are associated with underlying synchrony in energy demand, as measured by dynamic 2-deoxy-2-[ 18 F]fluoroglucose (FDG) positron emission tomography (PET). We measured absolute glucose metabolism, temporal metabolic connectivity (t-MC) and rfMRI patterns...

(Abstracted from JAMA 2017;317(2):129–130) This article highlights the risks associated with the use of marijuana during pregnancy. In the context of marijuana’s legalization in 29 states and Washington, DC, and the antinausea effects of tetrahydrocannabinol, the main psychoactive ingredient in it, there is an increased risk of pregnant women turni...

Representative Western blot bands. HIF-1α expression following 2-week or 4-week cocaine treatment, in different brain regions. (TIF)

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Cannabis is the most commonly used illicit drug in the United States,¹ and with the proliferation of states legalizing marijuana for medical and/or recreational purposes, attention has been focused on a potential rise in use and related problems. Primary attention has been on rates of use among youth, as early adolescent use has been linked to an i...

The role of the protein kinase Akt1 in dopamine neurotransmission is well recognized and has been implicated in schizophrenia and psychosis. However, the extent to which variants in the AKT1 gene influence dopamine neurotransmission is not well understood. Here we investigated the effect of a newly characterized variant number tandem repeat (VNTR)...

Cocaine induces vasoconstriction in cerebral vessels, which with repeated use can result in transient ischemic attacks and cerebral strokes. However, the neuroadaptations that follow cocaine’s vasoconstricting effects are not well understood. Here, we investigated the effects of chronic cocaine exposure (2 and 4 weeks) on markers of vascular functi...

Importance: Stimulant use disorder is common, affecting between 0.3% and 1.1% of the population, and costs more than $85 billion per year globally. There are no licensed treatments to date. Several lines of evidence implicate the dopamine system in the pathogenesis of substance use disorder. Therefore, understanding the nature of dopamine dysfunct...

Occurrence of transient ischemic attacks (TIA) and cerebral strokes is a recognized risk associated with cocaine abuse. Here, we use a rodent model along with optical imaging to study cocaine-induced TIA and the associated dynamic changes in cerebral blood flow velocity (CBFv) and cerebrovasculature. We show that chronic cocaine exposure in mice re...

The temporal dynamics of complex networks such as the Internet are characterized by a power scaling between the temporal mean and dispersion of signals at each network node. Here we tested the hypothesis that the temporal dynamics of the brain networks are characterized by a similar power law. This realization could be useful to assess the effects...

Cannabis enables and enhances the subjective sense of well-being by stimulating the endocannabinoid system (ECS), which plays a key role in modulating the response to stress, reward, and their interactions. However, over time, repeated activation of the ECS by cannabis can trigger neuroadaptations that may impair the sensitivity to stress and rewar...

[This corrects the article DOI: 10.1371/journal.pone.0155457.].

The overall premise of this review is that cerebrospinal fluid (CSF) is transported within a dedicated peri-vascular network facilitating metabolic waste clearance from the central nervous system while we sleep. The anatomical profile of the network is complex and has been defined as a peri-arterial CSF influx pathway and peri-venous clearance rout...

Drug-addiction may trigger early onset of age-related disease, due to drug-induced multi-system toxicity and perilous lifestyle, which remains mostly undetected and untreated. We present the literature on pathophysiological processes that may hasten aging and its relevance to addiction, including: oxidative stress and cellular aging, inflammation i...

PET allows noninvasive imaging of a variety of events in the body, including the activity of neuronal circuits in the brain that are involved in cognition and behaviors, by using radiotracers that detect relevant biological reactions. A major impediment to expanding PET applications to study the brain has been the lack of radiotracers that can iden...

The use of Positron emission tomography (PET) to study the effects of acute and chronic alcohol on the human brain has enhanced our understanding of the mechanisms underlying alcohol's rewarding effects, the neuroadaptations from chronic exposure that contribute to tolerance and withdrawal, and the changes in fronto-striatal circuits that lead to l...

Dopamine is involved in drug reinforcement but its role in addiction is less clear. In recent years, however, we have witnessed a dramatic advance in our understanding of dopamine's role in drug abuse in the human brain driven by the growing application of brain imaging techniques, including positron emission tomography (PET) and functional magneti...

Supplementary Figure 1 the brain regions which functional connectivity with dorsal posterior cingulate cortex showed significant association with trait urgency (PFWE = 0.05=, family-wise error (FWE) correction). (a) Seed region was defined from the Human Brainnetome Atlas (bilateral CG-6 region, L. Fan, 2016). (b) Seed region was anatomically defin...

Currently, 29 states and Washington, DC, have passed laws to legalize medical marijuana. Although evidence for the effectiveness of marijuana or its extracts for most medical indications is limited and in many cases completely lacking, there are a handful of exceptions. For example, there is increasing evidence for the efficacy of marijuana in trea...

Methamphetamine (MA) studies in animals usually involve acute, binge, or short-term exposure to the drug. However, addicts take substantial amounts of MA for extended periods of time. Here we wished to study the effects of MA exposure on brain and behavior, using an animal model analogous to this pattern of MA intake. MA doses, 4 and 8 mg/kg/day, w...

Objective: Postmortem brain studies support dysregulated expression of the histone deacetylase enzymes, HDAC1 and HDAC2, as a central feature in diseases including schizophrenia, bipolar disorder and depression. Our objective was to investigate HDAC expression in a large postmortem sample set representing healthy and disease brains. Methods: We use...

The effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, are a pressing concern for global mental health. Patterns of cannabis use are changing drastically owing to legalization, the availability of synthetic analogues (commonly termed spice), cannavaping and an emphasis on the purported therapeutic effects of can...

Neuroimaging studies have identified functional interactions between the thalamus, precuneus, and default mode network (DMN) in studies of consciousness. However, less is known about the structural connectivity of the precuneus and thalamus to regions within the DMN. We used diffusion tensor imaging (DTI) to parcellate the precuneus and thalamus ba...

Limited options for treating moderate-severe pain led to an overreliance on opioids and the current opioid epidemic. Addressing the factors contributing to a dearth of effective alternatives and re-energizing the development of pain therapeutics is necessary to quell this epidemic.

Neuroimaging techniques to measure the function and biochemistry of the human brain such as positron emission tomography (PET), proton magnetic resonance spectroscopy (1H MRS), and functional magnetic resonance imaging (fMRI), are powerful tools for assessing neurobiological mechanisms underlying the response to treatments in substance use disorder...

Unaccounted temporal dynamics of resting-state functional connectivity (FC) metrics challenges their potential as biomarkers for clinical applications in neuroscience. Here we studied the scan time required to reach stable values for various FC metrics including seed-voxel correlations and spatial independent component analyses (sICA), and for the...

Drug addiction represents a dramatic dysregulation of motivational circuits that is caused by a combination of exaggerated incentive salience and habit formation, reward deficits and stress surfeits, and compromised executive function in three stages. The rewarding effects of drugs of abuse, development of incentive salience, and development of dru...

In Reply We appreciate the additional points that Solowij et al contribute to this important discussion.¹ The uncertainty regarding the relationship between exposure parameters and neural substrates on one hand and persistence or decay of cognitive impairment and the associated neurobiological changes on the other is indeed a critical and challengi...

Because of the overall high prevalence and marked increases in morbidity and mortality associated with nonmedical prescription opioids and heroin, addressing opioid use disorders is a public health priority in the United States.1 In 2014, 10.3 million persons reported using prescription opioids nonmedically (ie, using medications that were not pres...

Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum o...

Alcohol abuse is a chronic disease characterized by the consumption of alcohol at a level that interferes with physical/ mental health and cause serious and persistent changes in the brain. Lipid metabolism is of particular interest due to its high concentration in the brain. Lipids are the main component of cell membranes, are involved in cell sig...

The extent to which cannabis is deleterious to the human brain is not well understood. Here we test whether cannabis abusers have impaired frontal function and reactivity to dopaminergic signaling, which are fundamental to relapse in addiction. We measured brain glucose metabolism using PET and [(18)F]FDG both at baseline (placebo) and after challe...

Data-driven functional connectivity density (FCD) mapping is being increasingly utilized to assess brain connectomics at rest in the healthy brain and its disruption in neuropsychiatric diseases with the underlying assumption that the spatiotemporal hub distribution is stationary. However, recent studies show that functional connectivity is highly...