Striatocortical Pathway Dysfunction in Addiction And Obesity: Differences and Similarities (2013) Nora Volkow

. Author manuscript; available in PMC 2014 Jan 1.

PMCID: PMC3557663



Neuroimaging techniques are starting to reveal significant overlap in the brain circuitry underlying addiction and disorders of dyscontrol over rewarding behaviors (such as binge eating disorder and obesity). Positron emission tomography (PET) has demonstrated impaired striatal dopamine (DA) signaling (decreased D2 receptors) in drug addiction and obesity that is associated with reduced baseline glucose metabolism in medial and ventral prefrontal brain regions. Functional magnetic resonance imaging (fMRI) has documented brain activation abnormalities that also implicate DA-modulated striato-cortical pathways. In this review we map findings from recent neuroimaging studies that differentiate brain activation in drug/food addiction from those in controls within brain networks functionally connected with ventral and dorsal striatum. We show that regions found to be abnormal in addiction and obesity frequently emerge at the overlap of the dorsal and the ventral striatal networks. Medial temporal and superior frontal regions functionally connected with dorsal striatum display greater vulnerability in obesity and eating disorders than in drug addictions, indicating more widespread abnormalities for obesity and eating disorders than for addictions. This corroborates involvement of both ventral striatal (predominantly associated with reward and motivation) and dorsal striatal networks (associated with habits or stimulus response learning) in addiction and obesity but also identify distinct patterns between these two disorders.

Dopamine (DA) encodes prediction signals for natural and drug reinforcers and facilitates conditioning (learning of reward associations) by modulating brain activity in subcortical and cortical regions (). Drugs of abuse are compulsively consumed by humans or self-administered by laboratory animals because they are inherently rewarding (;). Drugs of abuse have been shown to cause abrupt increases in extracellular DA in the striatum () that parallel the time course of the subjective “high” (). However, other neurotransmitters such as cannabinoids and opioids, and neuropeptides also play important roles in reward and addiction and are intimately involved in triggering the neuroplastic changes that follow repeated drug use and involve changes in glutamatergic signaling in striatocortical pathways (;;). Preclinical and clinical studies assessing the response to drug/food cues have shown increases in extracellular DA in striatum that were associated with enhanced motivation to consume drugs/foods. This evidences the involvement of DA in cue-induced overeating, just as it has been shown to underlie its involvement in cue-induced relapse in drug addiction (;). Thus, it has been postulated that DA-modulated circuits showing drug-related impairments in drug addiction could also be implicated in pathologic, compulsive eating behaviors (;).

During the last two decades positron emission tomography (PET) studies have evaluated the role of DA in association with glucose metabolism in reward and addiction (;;). The role of striatal DA on baseline brain activity, on the responses to drugs and on the responses to drug cues, has been studied with PET technology using multiple tracer approaches in both addicted and non addicted individuals (Fig 1). The combined use of D2 receptor (ie., [11C]raclopride, [18F]n-methylspiroperidol) and DA transporter (such as [11C]cocaine, [11C]d threo-methylphenidate) radioligands with fludeoxyglucose ([18F]FDG, ligand used to measure brain glucose metabolism) demonstrated that the availability of DA D2 receptors (D2R) and transporters (DAT) in striatum is associated with metabolic activity in frontal and temporal cortices (;;;) (Fig 2). These studies have consistently demonstrated impaired DA function in striatum (decreases in D2R, reduced DA release) and its association with reduced baseline glucose metabolism (marker of brain function) in frontal (orbitofrontal cortex, anterior cingulate, dorsolateral prefrontal) and temporal cortices (most notable in insula) ().

Fig 1 

Striatal DA neurotransmission abnormalities in addiction and obesity
Fig 2 

Association between brain metabolism and DA neurotransmission: (A) Statistical axial maps of correlations between relative glucose metabolism and DA D2 receptors (D2R) in the striatum for subjects with a family history of alcoholism and (B) scatter plots

In parallel functional magnetic resonance imaging (fMRI) studies have assessed changes in brain function and connectivity in addicted subjects (). The role of brain activation has been studies with fMRI using the endogenous blood-oxygenation-level-dependent (BOLD) contrast () and a plethora of task activation paradigms. These studies have shown that addiction affects not only the reward circuit, but also brain regions involved in attention, memory, motivation, executive function, mood and interoception ().

More recently, PET and fMRI multimodality studies have documented an association between DA neurotransmission in striatum and fMRI responses in the default mode network (DMN; including ventral prefrontal cortex and precuneus) (;) that deactivates during task performance in healthy controls (;) (Fig 2). Pharmacological fMRI studies using stimulant drugs with DA enhancing effects such as modafinil and methylphenidate have also suggested an association between DA signaling and DMN function (;). Other pharmacological PET and fMRI studies demonstrated that stimulants (methylphenidate) can attenuate limbic brain responses to cocaine cues () and normalize fMRI responses during a cognitive task (;) in cocaine addicts. However, the association between impaired DA neurotransmission and abnormal activation in addiction and obesity is still poorly understood.

Dopaminergic responses to drugs and food

All addictive drugs display ability to increase DA in striatum, particularly in the nucleus accumbens (ventral striatum), which underlies their rewarding effects (). DA neurons located in the ventral tegmental area (VTA) and substantia nigra (SN) in the midbrain project to the striatum via the mesolimbic and nigrostriatal pathways. The rewarding and conditioning effects of drugs (and very likely to food too) seem to be predominantly driven by transient and pronounced increases in DA cell firing () that result in high DA concentrations that are necessary to stimulate the low affinity D1 receptors (). In humans, PET studies have shown that several drugs increase DA in dorsal and ventral striatum and that these increases are associated with the subjective rewarding effects of the drugs [stimulants (;), nicotine (), alcohol () and cannabis ()]. Dopaminergic responses might also play a role in the rewarding effects of foods and contribute to excessive consumption and obesity (). Certain foods, particularly those rich in sugars and fat, are potently rewarding and can promote over-eating () because like drugs they increase striatal DA release (). Moreover, food can increase DA in ventral striatum solely on the basis of its caloric content and independent of palatability (). Whereas food-reward associations were advantageous in environments where food sources were scarce and/or unreliable, this mechanism is now a liability in our modern societies where food is plentiful and constantly available.

Other neurotransmitters than dopamine (cannabinoids, opioids, and serotonin) as well as neuropeptide hormones (insulin, leptin, ghrelin, orexin, glucagon like peptide, agouti related protein, PYY) have been implicated in the rewarding effects of food and in the regulation of food intake (;;). Furthermore, food-related striatal DA increases alone cannot explain the difference between normal food intake and excessive compulsive food consumption since these also occur in healthy individuals who do not overeat. Therefore, as for addiction, downstream adaptations are likely to be involved in the loss of control over food intake. These neuroadaptations might lead to decreases in tonic DA cell firing, enhanced phasic DA cell firing in response to drug or food cues and reduced executive function including impairments in self-control (;).

Striatocortical connectivity

Cortical correlates of striatal dopaminergic deficits in addition are not unexpected. Anatomical studies in non-human primates and in rodents documented that motor, somatosensory and dorsolateral prefrontal cortices project to dorsal striatum (;;;;;), and that anterior cingulate (ACC) and orbitofrontal (OFC) cortices project to ventral striatum (;;;;;).

Recently, Di Martino and colleagues were able recapitulate these striatocortical circuits using brief (< 7 min) MRI scanning sessions at rest in 35 human subjects () and supported a meta-analysis of PET and fMRI studies that identified functional connectivity between the anterior dorsal striatum and the insula (). Resting state functional connectivity (RSFC) is advantageous when studying patients with functional deficits because the data is collected at rest avoiding performance confounds (task stimulation paradigms require the subjects’ cooperation and motivation), and has potential as a biomarker for diseases that affect the brain DA system.

Recent studies have documented impairments in functional connectivity both in drug addiction and in obesity. Specifically lower functional connectivity has been reported between dopaminergic midbrain nuclei (VTA and SN) with striatum and with the thalamus (;), between the hemispheres (), and between the striatum and cortex () in cocaine addicts. Abnormal striato-cortical connectivity was also documented in social drinkers (), opioid abusers (;;;) and obese subjects (;;). Overall, these studies suggest that abnormal connectivity between cortical and subcortical regions might underlie the pathological states in drug addiction and obesity. Open access to large RSFC databases integrating datasets from multiple studies promises increased statistical power and sensitivity to characterize the connectivity of the human brain (;). Here we reproduce the RSFC patterns from dorsal and ventral striatal seeds documented by Di Martino and colleagues () in a large sample of healthy subjects. The coordinates of the abnormal clusters documented by previous neuroimaging studies on food/drug addiction were projected into these striatal networks to assess their implication in addiction and obesity. Other striatal seed regions (i.e. dorsal caudate) were unnecessary because their functional connectivity patterns were largely included within the union of the ventral and dorsal RSFC patterns.

The RSFC patterns were computed using the three largest datasets (Beijing: N=198; Cambridge: N=198; Oulu: N=103) of the public image repository “1000 Functional Connectomes Project” (, which included a total of 499 healthy subjects (188 males and 311 females; age: 18-30 years). We used the approach by Di Martino et al. to map dorsal and ventral striatal networks. The standard image post processing (realignment and spatial normalization to the MNI space) was carried with the statistical parametric mapping package (SPM5; Wellcome Trust Centre for Neuroimaging, London, UK). Then, seed-voxel correlation analysis with Gram-Schmidt orthogonalization (;) was used to compute the functional connectivity of the bilateral dorsal (x = ±28 mm, y = 1 mm, z = 3 mm) and ventral (x = ±9 mm, y = 9 mm, z = -8 mm) striatal seed regions (0.73ml cubic volumes). In addition, the functional connectivity of a bilateral primary visual cortex seed (x = ±6 mm, y = -81 mm, z = 10 mm; calcarine cortex, BA 17) was computed as a control network. These RSFC maps were spatially smoothed (8-mm) and included in a voxel-wise one-way analysis of variance (ANOVA) SPM5 model, independently for dorsal and ventral striatal seeds. Voxels with T-score > 3 (p-value < 0.001, uncorrected) were considered to be significantly connected to the seed regions and were included as part of the networks.

The RSFC pattern of the dorsal striatal seeds (Fig 3) was bilateral and included dorsolateral prefrontal (BAs: 6, 8, 9, 44-46), inferior (BA: 47) and superior frontal (BAs: 8-10), temporal (BAs: 20, 22, 27, 28, 34, 36-38, 41-43), inferior and superior parietal (BAs: 2, 3, 4, 5, 7, 39, 40), occipital (BA: 19), and cingulate (BAs: 23, 24, 32), occipital (BA 19) and limbic (BA: 30) cortices, thalamus, putamen, globus pallidus, caudate, midbrain, pons, and cerebellum. The RSFC pattern of the ventral striatal seeds was also bilateral and included ventral orbitofrontal (BA: 11), superior frontal (BAs: 8-10), temporal (BAs: 20, 21, 27-29, 34, 36, 38), inferior parietal (BA: 39), and cingulate (BAs: 23-26, 32) and limbic (BA: 30) cortices, thalamus, putamen, globus pallidus, caudate, midbrain, pons, and cerebellum. These ventral and dorsal patterns overlapped in inferior (BA: 47) and superior frontal (BAs: 9), temporal (BAs: 20, 27, 28, 34, 36, 38), cingulate (BAs: 23, 24, 32) and limbic (BA: 30) cortices, thalamus, putamen, globus pallidus, caudate, midbrain, pons, and cerebellum. Thus, there was significant overlap as well as significant differences between these dorsal and ventral network patterns that corroborate those from Di Martino et al () and are consistent with the patterns reported by anatomical studies (). The RSFC pattern of the primary visual cortex (V1) was also bilateral and included occipital (BAs 17-19), temporal (BA 37), superior parietal (BA 7), auditory (BAs 22 and 42) and premotor (BA 6) cortices and bilateral posterior superior cerebellum (Fig 3). Thus, the V1 connectivity pattern was smaller (volume of the V1 network = 16% gray matter volume) and partially overlapped the dorsal striatal network (6% gray matter volume in BAs 6, 7, 19 and 37) but not the ventral striatal network.

Fig 3 

RSFC networks from dorsal and ventral striatum


In what follows we review functional neuroimaging studies on alcohol, cocaine, methamphetamine, and marijuana (Tables 1​-4),4), as well as obesity and eating disorders (Tables 5 and ​and6)6) that were published between January 1, 2001 and December 31, 2011; nicotine addiction was not included because there were only five fMRI studies on nicotine addiction and none assessed brain activation differences between smokers and non-smokers. The words “activation”, “connectivity”, “dopamine”, “cocaine”, “marijuana”, “cannabis”, “methamphetamine”, “alcohol”, “PET”, and “MRI” were included in a search of peer-reviewed publications in PubMed ( to identify relevant brain imaging studies. Only studies that reported the spatial coordinates of the clusters (in the Montreal Neurological Institute (MNI) or Talairach stereotactic frames of references) showing significant activation/ metabolic differences between drug users/obese patients and controls (P < 0.05, corrected for multiple comparisons) were included in the analysis.

Table 1 

Summary of functional magnetic resonance imaging studies (conducted between 2001 and 2011) on effects of alcohol addiction on brain function that were included in Figs 4 and ​and5.5. Studies are grouped by stimulation paradigms into four major
Table 4 

Summary of functional magnetic resonance imaging studies (conducted between 2001 and 2011) on effects of marijuana addiction on brain function included in Figs 4 and ​and5.5. Studies are grouped by stimulation paradigm into four major categories.
Table 5 

Summary of functional magnetic resonance imaging studies (conducted between 2001 and 2012) on effects of obesity on brain function included in Figs 4 and ​and6.6. Studies are grouped by stimulation paradigm into two major categories. Number of
Table 6 

Summary of functional magnetic resonance imaging studies (conducted between 2001 and 2011) on effects of eating and eating disorders on brain function included in Figs 4 and ​and6.6. Number of patients (S) and control (C) subjects and tasks are

A coordinate-based meta-analysis was used to evaluate the degree of agreement between studies. We used an activation likelihood estimation approach () to build likelihood functions for each reported cluster. Specifically, a 3D Gaussian density (15-mm full-width-half-maximum) was centered at the MNI coordinates of each cluster that reported significant activation differences with respect to controls for drug users, obese individuals and eating disorder patients, regardless if they were increases or decreases. The SPM5 one-way ANOVA was used to analyze the statistical significance of the likelihood maps (3-mm isotropic resolution) corresponding to the 44 studies on drug addiction (Tables 1​-4),4), and the 13 studies on obesity and eating disorders (Tables 5 and ​and6).6). The meta-analysis showed that the anterior and middle cingulate cortices frequently demonstrate activation abnormalities in neuroimaging studies on drug addiction, and that the putamen/posterior insula, hippocampus, superior prefrontal cortex (PFC), middle and inferior temporal cortices and cerebellum frequently demonstrate activation abnormalities in studies on obesity and eating disorders (PFWE < 0.05, corrected for multiple comparisons in the whole brain using the random field theory with family-wise error correction; Fig 4; Table 7). This meta-analysis also showed that the likelihood of abnormal activation findings in putamen/posterior insula, hippocampus, parahippocampus and temporal cortices is usually higher for studies on obesity and eating disorders than for studies on drug addiction (PFWE < 0.05; Fig 4; Table 7). In ACC (BA 24 and 32), PFC (BA 8), putamen/posterior insula, hippocampus (BA 20), cerebellum, middle and superior temporal (BAs 21, 41 and 42) and supramarginal gyri the strength of the functional connectivity was stronger for the dorsal than for the ventral striatum and in the anterior medial frontal cortex (BAs 10 and 11) was stronger for the ventral than for the dorsal striatum (PFWE < 0.05; Table 7).

Fig 4 

Coordinate-based meta-analysis of neuroimaging studies on drug addiction, obesity and eating disorders
Table 7 

Coordinate-base meta-analysis of neuroimaging studies on drug addiction, obesity and eating disorders published between 2001 and 2011 (Tables 2-7). MNI coordinates (x, y, z) and statistical significance (T-score) for clusters that demonstrated significant


In alcoholics, postmortem studies and brain imaging studies have reported reductions in D2R in striatum, including NAc (). fMRI studies on alcoholics have reported abnormal responses to cue-reactivity, working memory, inhibition, and emotional paradigms in cortical and subcortical brain regions (Table 1). During cue-reactivity or with exposure to alcohol, more than 67% of the activation clusters that differentiated alcoholics from controls were included in the striatal networks (Fig 5). For instance, intravenous ethanol increased activation in ventral striatum and other limbic areas in social drinkers but not in heavy drinkers () and alcohol taste cues activated PFC, striatum and midbrain in heavy drinkers (). Alcohol sips increased fMRI activation in dorsolateral PFC (DLPFC) and anterior thalamus when alcoholics were exposed to alcohol cues (). Alcoholics also demonstrated higher fMRI activation than controls in putamen, ACC and medial PFC and decreases in ventral striatum and PFC when viewing alcohol/control cues (;). Clusters reporting alcohol-related activation abnormalities during cue-reactivity tasks were more frequently located in the “overlapping” network defined by the intersection of the dorsal and ventral networks (Fig 3, magenta; 21% of the gray matter volume) than in regions that were functionally connected to V1, regardless if they overlapped (yellow) or not (green) with the striatal networks. These data suggests that exposure to alcohol-associated cues engage the intersection of the ventral and dorsal striatal networks in agreement with PET findings showing deficits in ventral and dorsal striatal D2R and in DA signaling in alcoholics ().

Fig 5 

Relative number of abnormal clusters per network: Drug addiction

The striatal networks also included a large fraction of alcohol-related findings for working memory and memory encoding tasks. To assess the effect of alcohol intoxication on cognitive function, Gundersen et al. evaluated fMRI activation during n-back working memory when subjects drank alcohol versus when they drank soft drinks. They found that acute alcohol intake decreased activation in dorsal ACC and cerebellum, and that these decreases varied with cognitive load and blood alcohol concentrations (). Alcoholics assessed with a working memory task demonstrated weaker lateralization of fMRI activation in parahippocampal regions, supporting the hypothesis that the right hemisphere is more vulnerable to alcohol-related damage than the left one (), and increased ACC activation compared to controls (). More than 90% of the alcohol-related activation findings occurred in the striatal networks. These findings strongly support an association between activation abnormalities during working memory and striatal dysfunction in alcoholics.

The striatal networks also included a significant fraction of alcohol-related findings in studies on emotion and inhibitory control. During anticipation of monetary gain detoxified alcoholics exhibited lower activation in ventral striatum than controls but showed higher striatal activation during alcohol-cue exposure, which were correlated with alcohol craving in alcoholics but not in controls (). Studies on adolescents at risk for alcoholism (children of alcoholics, or COA) reported higher activation in dorsomedial PFC and less activation in ventral striatum and amygdala for alcohol-vulnerable subjects than for alcohol-resilient controls (). Studies on impulsivity reported greater fMRI activation in DLPFC and ACC during the Stroop interference test (), and lower deactivation in ventral striatum, ventral PFC, and OFC during an inhibitory go/no-go task () for COA than for control adolescents. The high prevalence of findings within the striatal networks during these studies (> 83%) strongly suggests that alcohol vulnerability and related impairments in inhibitory capacity and control mechanisms are associated with striatal dysfunction. Indeed, we documented higher than normal availability of D2R in dorsal and ventral striatum associated with normal function in prefrontal brain regions (OFC, ACC, DLPFC) and anterior insula in COA who were not alcoholics as adults (Figure 2) (). We postulated that the striatal increases in D2R enabled them to maintain normal function in prefrontal brain regions, protecting them against alcoholism.


The striatal networks captured 83% of the abnormal activation clusters in cocaine subjects suggesting cortico-striatal dysfunction in cocaine addiction. Drug cues (words) showed lower fMRI activation in rostral ventral and caudal dorsal ACC than neutral words in cocaine addicts () who showed lower activation than controls in these ACC regions () but higher activation in midbrain (). Administration of the DA enhancing medication methylphenidate (20 mg oral) normalized the hypo ACC activation in cocaine addicts (). During a cocaine-cue video, brain activation in left DLPFC and bilateral occipital cortex was stronger for cocaine subjects than for healthy controls (). However, glucose metabolism in left insula, OFC and NAc, and right parahippocampus was lower when cocaine subjects watched a cocaine-cue video than when they watched a neutral-cue video and methylphenidate (20 mg, oral) reduced the abnormal response to the cocaine-cues (). When instructed to inhibit their craving prior to exposure to cocaine-cues, cocaine abusers were able to reduce metabolism of the OFC and NAc (compared to the condition when they did not aim to control their craving), an effect that was predicted by baseline metabolism in the right inferior frontal cortex (BA 44) (). In cocaine addicted women, but not in men, exposure to cocaine-cues (video and measured with PET and FDG) was associated with a significant reduction in metabolism in cortical brain regions that are located within the striatal networks and are also part of the control networks (). Inasmuch as DA modulates control networks through striatal cortical pathways these findings support the involvement of control networks in addiction. Upon exposure to the stimulant drug itself (intravenous methylphenidate, which cocaine abusers reported to have similar effects to those of intravenous cocaine) cocaine abusers showed increased metabolic activation in OFC and ventral cingulate whereas control subjects decreased metabolic activity in these regions ().

The striatal networks also captured 71% of cocaine-related abnormal activation clusters during working memory and visual attention tasks and the control regions (functionally connected to V1) that overlapped the dorsal striatal network (Fig 3, yellow) had much higher likelihood of abnormalities than those that did not overlap the striatal networks (green). During verbal n-back working memory cocaine subjects demonstrated lower activation in thalamus and midbrain, dorsal striatum, ACC, and limbic regions (amygdala and parahippocampus) and hyper activation in PFC and parietal cortices (). Some of these abnormalities were accentuated in the cocaine abusers with positive urines for cocaine at time of study suggesting that the deficits may reflect in part early cocaine abstinence (). Indeed, during early abstinence treatment-seeking cocaine-dependent individuals exhibited hypo activation in striatum, ACC, inferior PFC, precentral gyrus, and thalamus compared to controls (). Other studies on working memory reveled that cocaine cues can increase brain activation in occipital cortex (). During visual attention tasks, cocaine abusers had lower thalamic activation and higher occipital cortex and PFC activation than controls (). The association between cortico-striatal dysfunction and abnormal fMRI activation during memory and attention tasks occurred predominantly at the intersection of the dorsal and ventral networks, which had 3 times higher likelihood (relative number of cluster normalized by network volume) than regions not functionally connected to the striatum (Fig 5).

During decision-making with the Iowa gambling task cocaine abusers demonstrated higher regional cerebral blood flow (rCBF; measured with 15O-water PET) in right OFC and lower rCBF in DLPFC and medial PFC compared to controls (). During a forced-choice task under three monetary value conditions cocaine subjects showed lower fMRI responses to monetary reward in OFC, PFC and occipital cortex, midbrain, thalamus, insula and cerebellum (). Lower than normal D2R availability in dorsal striatum was associated with decreased thalamic activation responses whereas in ventral striatum it was associated with increased medial PFC activation in cocaine addicted individuals (). Similarly to cognitive tasks, findings at the intersection of the dorsal and ventral networks exhibited higher likelihood than those in regions not functionally connected to the striatum.

Sixty-four % of the brain clusters reported by fMRI studies on inhibitory tasks were included in the striatal networks. During go/no-go inhibition cocaine addicts demonstrated lower activation than controls in OFC, supplementary motor area and ACC, regions that might be critical for cognitive control (). Short- and long-term abstinent cocaine users exhibited differential activation in PFC, temporal cortex, cingulum, thalamus and cerebellum (). During different inhibitory tasks (Stroop interference) cocaine addicts showed lower rCBF in left ACC and right PFC, and higher rCBF in right ACC than controls (). Striatal functional connectivity failed to explain brain activation differences from studies that used stop-signal tasks (). These studies showed lower activation in ACC, parietal and occipital cortices in cocaine abusers. PET studies measuring mu opioid receptors (using [11C]carfentanil) showed higher specific binding in frontal and temporal cortices for one-day abstinent cocaine dependent subjects than for controls, and these abnormalities decreased with abstinence and correlated with cocaine use (;).


Compared to control subjects, metamphetamine abusers tested during early detoxification demonstrated decreased glucose metabolism in striatum and thalamus whereas they showed increased activity in parietal cortex (). This suggested that both DA as well as non DA modulated brain regions are affected by chronic metamphetamine consumption (). Moreover decreased striatal DA activity was associated with a greater likelihood of relapse during treatment (), protracted abstinence was associated with partial recovery of striatal DAT () and of regional brain metabolism (), and reductions in striatal D2R were also associated with reduction in metabolism in OFC in recently detoxified methamphetamine abusers ().

A large fraction (70%) of the methamphetamine-related fMRI findings was encompassed by the striatal networks (Fig 5). When compared to controls, methamphetamine dependent individuals exhibited higher ACC activation during go/no-go response inhibition (), and lower right PFC activation during Stroop interference (). Most of these abnormal activation clusters (88%) occurred within the dorsal network (including its overlap with the ventral network). During decision-making, however, a lower fraction (64%) of the clusters was encompassed by the striatal networks. Using a two-choice prediction task, Paulus and colleagues found that fMRI activation was lower in PFC (), OFC, ACC and parietal cortex for methamphetamine-dependent subjects than for controls (). Moreover, a combination of activation responses in these regions best predicted the time to relapse and showed different activation patterns as a function of error rate in left insula and DLPFC ().


The involvement of striatal dysfunction in marijuana addiction is less clear because neither baseline striatal D2R nor striatal DA release (after amphetamine challenge) abnormalities were observed in recent PET studies with [11C]raclopride (;). An FDG study showed that when given tetrahydrocannabinol (THC) chronic marijuana abusers showed increases in OFC and medial PFC and in striatum whereas controls did not, but it increased cerebellar metabolism in both abusers and controls suggesting that striatal networks are involved in marijuana addiction (). Tactile marijuana-related cues versus neutral cues were shown to increase fMRI activation in VTA, thalamus, ACC, insula, and amygdala, supporting the involvement of striatal networks, as well as in other prefrontal, parietal and occipital cortices and cerebellum in recently abstinent marijuana users (). During a visual attention task, marijuana abusers had lower fMRI activation in right PFC, parietal cortex and cerebellum (normalized with duration of abstinence) and higher activation in frontal, parietal and occipital cortices than controls (). During working memory, however, marijuana abusers exhibited decreased activation in temporal lobes, ACC, parahippocampus and thalamus with increased task performance, a group × performance interaction effect that was opposite in controls (). During go/no-go inhibition, adolescents with histories of marijuana use showed higher fMRI activation in DLPFC, parietal and occipital cortices, and insula than adolescents without histories of marijuana use (). During visuomotor integration with a visually paced finger sequencing task cued by a flashing checkerboard, marijuana users had higher PFC activation and lower visual cortex activation than controls (). Sixty-nine % of the abnormal activation clusters in studies on effects of marijuana on brain function were located in regions functionally connected to the striatum.


Compulsive-like feeding behavior in obese rats has been associated with downregulation of striatal D2R () and obesity has been linked to lower striatal D2R in humans (), suggesting that common neuroadaptations in DA striatal pathway may underlie obesity and drug addiction. Baseline PET studies of brain glucose metabolism in obese individuals reported reductions in metabolic activity in OFC and ACC that were associated with lower than normal striatal D2R availability ().

Brain activation in dorsal and ventral striatum, insula, hippocampus, OFC, amygdala, medial PFC and ACC elicited by visual exposures to high caloric foods was higher for obese than for control women (;). Similarly, visual food cues elicited increased fMRI activation responses in frontal, temporal, and limbic regions for obese adults than for controls (), and hippocampal activation showed a correlation with fasting plasma levels of insulin and waist circumference in adolescents (). Striatal activation in response to chocolate milkshake intake was associated with gains in body weight and with the presence of the A1 allele of the TaqIA restriction fragment length polymorphism, which is associated with D2R gene binding in the striatum and compromised striatal DA signaling (). Adolescents with high risk for obesity showed higher activation in caudate and operculum in response to chocolate milkshake intake than those with low risk for obesity (). During gastric distention, as it occurs during meal ingestion, obese subjects had increased fMRI activation than normal weight subjects in cerebellum and posterior insula and decreased activation in amygdala, midbrain, hypothalamus, thalamus, pons, and anterior insula (). Eighty-two % of the activation clusters from these studies on cue-reactivity occurred in regions functionally connected to the striatum (Fig 6). Consistent with these activation response PET studies measuring D2R with [18F]fallypride in obese subject showed an inverse correlation between ghrelin and D2R in dorsal and ventral striatum and in inferior temporal cortex, temporal pole, insula and amygdala ().

Fig 6 

Relative number of abnormal clusters per network: Obesity and eating disorders

Food perception and control of food intake

In normal conditions food intake is thought to be determined by both homeostatic (balance of energy and nutrients in the body) and non-homeostatic (pleasure of eating) factors, and brain DA has been associated with eating behaviors (). Pharmacological fMRI studies have shown that hypothalamic activation predicts food intake when the plasma level concentration of PYY, a peptide hormone that provides a physiological gut-derived satiety signal to the brain, is low and that activation in OFC striatum, VTA, SN, cerebellum, PFC, insula and cingulum can predict feeding behavior when PYY plasma level concentration is high ().

Event-related studies contrasting brain responses to sucrose taste and tasteless water showed that hunger was associated with fMRI activation in insula, thalamus, cerebellum, cingulum, SN as well as cortical brain regions whereas satiety was associated with deactivation in parahippocampus, hippocampus, amygdala and ACC (). In this study the differential effect of hunger versus satiety on brain activation to taste stimuli (salty, sour, bitter, sweet) was stronger for males than for females, particularly in dorsal striatum, amygdala, parahippocampus and posterior cingulum (). PET studies on inhibitory control in hunger conditions that used real food stimulation revealed that purposeful inhibition of the desire for food decreased glucose metabolism in amygdala, hippocampus, insula, striatum and OFC in men but not in women (). A large fraction (> 31%) of the activation clusters occurred in regions functionally connected to both dorsal and ventral striatum (Fig 6, magenta).

Eating disorders

Pharmacological studies have shown that disruption of DA signaling in the striatum can inhibit normal feeding in rodents (;) and that DA signaling modulates reactivity to food cues in humans (). PET studies of patients suffering from anorexia (over control of eating habits) showed higher than normal striatal D2R availability (). In contrast, a recent study in non-obese patients with binge eating disorder showed that while they did not differ in D2R availability from controls they showed enhanced striatal DA release during food stimulation (). fMRI studies showed that when exposed to pleasant food pictures patients with binge eating disorder had stronger medial OFC responses that controls whereas patients with bulimia nervosa had stronger ACC and insula responses than controls (). During go/no-go inhibition, binge eating/purging female adolescents showed higher activation in temporal cortex, PFC and ACC than controls, and anorexia nervosa patients exhibited higher activation in hypothalamus and lateral PFC (). Since only one of these clusters was located outside the striatal networks, these data also corroborates a role of cortico-striatal networks in eating disorders.

Prefrontal regions

The prefrontal cortex and the striatum are inter modulated via cortico-striatal networks modulated by DA (). The frontal cortex plays a complex role in cognition, including inhibitory control, decision making, emotional regulation, purposefulness, motivation and salience attribution among others. It has been hypothesized that dysfunctions in frontal regions might impair the control over compulsive drug intake (;), and that frontal cortex disruptions can have serious consequences in drug addiction ().

The frontal abnormalities revealed by our meta-analysis are consistent with the correlations between striatal D2R reductions and decreased metabolic activity in ACC, OFC and DLPFC previously reported for cocaine and methamphetamine abusers and alcoholics (;;). Since ACC, lateral OFC and DLPFC are involved with inhibitory control and decision making (;), this association suggests that loss of control over drug intake () could reflect improper DA-regulation in these frontal regions. This hypothesis is supported by studies that associated striatal D2R reductions and impulsivity scores in methamphetamine abusers () and rodents () and by those that linked ACC impairments with obsessive compulsive behaviors and impulsivity (). However, another possibility is that early abnormalities in frontal regions trigger repeated drug use and neuroadaptations that decrease striatal D2R. For instance, non-alcoholic individuals with a family history of alcoholism had higher than normal striatal D2R that was associated with normal metabolism in ACC, OFC and DLPFC, suggesting that that normal activity in prefrontal regions promoting inhibitory control and emotional regulation could be the mechanism that protected these subjects against alcohol abuse (). Interestingly, a recent study that compared sibling discordant for stimulant addiction showed significant differences in volume of medial OFC (), suggesting that these differences reflected the exposure to the drug rather than genetic vulnerability ().

Temporal regions

The striatum is also connected with medial temporal lobe structures (hippocampus parahippocampal gyrus) that are essential for explicit memory but also for conditioning (). Brain activation studies on reward-motivated learning have documented the involvement of medial temporal lobe structures in subsequent memory enhancements (;). Thus drug cues could trigger craving memory activating learning circuits in the medial temporal cortex, and this enhanced activation of memory circuits could contribute to overcome the inhibitory control exerted by the prefrontal cortex in food and drug addiction (). Our meta-analysis revealed that drug addiction, obesity and eating disorders are characterized by common brain activation abnormalities in medial temporal cortex (hippocampus, parahippocampal gyrus and amygdala), superior and inferior temporal cortices and posterior insula (PFWE< 0.05). The pattern of brain activation abnormalities partially overlapped the dorsal (40%), ventral (10%) and overlapping (48%) networks; only 2% of the abnormalities did not show overlap with the striatal networks. Our meta-analysis also revealed stronger abnormalities in medial temporal lobe structures in obesity and eating disorders compared to drug addiction (Fig 4). This suggests that these temporal regions are involved in the regulation of eating behaviors to a greater extent than in the regulation of drug intake. Specifically food intake is regulated both by homeostatic and reward pathways and while the homeostatic system modulates the reward pathway, it also modulates other brain regions through the various peripheral hormones and neuropeptides that regulate hunger and satiety. Indeed medial temporal regions (hippocampus, parahippocampus) express leptin receptors () and insulin-like growth factor receptors () as well as mRNA for the ghrelin receptor gene (). Thus greater involvement of medial temporal cortices in obesity than in addiction is consistent with the involvement of hormones and neuropeptides that regulate food intake via the homeostatic pathway.

Reward and habits

For both drug and food intake reward processes in ventral striatum initially drive the motivation to repeat the behavior. However with repeated exposure conditioned responses and learned associations shift the incentive motivation to the conditioned stimulus that predicts the reward. This transition, along with the associated enhanced motivation to do the behaviors necessary to consume the reward (drug or food), requires involvement of the dorsal striatum (). In addition, repeated exposure to associated pairing results in habits that can further drive behavior (including eating or taking drugs or alcohol) also involve dorsal striatal regions. However in reviewing the significant overlap between ventral and dorsal striatal connectivity it is therefore not surprising that studies show activation of ventral and dorsal striatum both with reward and conditioning. Similarly while the dorsal striatum is predominantly associated with habits their formation may also require a progression from ventral to dorsal striatal regions ().

Vulnerable networks in addiction and obesity

An important finding from this study is that functional abnormalities in food or drug addiction tend to occur in brain regions functionally connected to both dorsal and ventral striatum. These vulnerable regions are essential for cognitive control (anterior cingulum and supplementary motor area), reward and motivation (striatum and medial OFC) and reward-motivated learning (hippocampus and parahippocampal gyrus). The overlap of striatal connectivity patterns suggests that dopaminergic modulation from both dorsal and ventral striatum is essential in these regions, and their higher vulnerability suggests that food/drug addiction might alter delicate striatal modulation balance and brain activation in these regions.


Our meta-analysis includes studies on acute effects of drugs and food (cues), as well as studies on cognition (memory, attention, inhibition, decision-making) and emotion when drugs or food are not present. Since the direct and the long-term effects of food/drug addiction are different the participants in the former studies may or may not be the most vulnerable to brain changes. These could have increased the variability, limiting the interpretation of the results. The over expression of the medial temporal lobe abnormalities in obesity and eating disorders compared to those in drug addiction may reflect the severity of the disorders as it is not easy to equate intensity, duration or age of initiation of the disorder.

In summary this analysis of recent brain imaging studies on different types of drug addiction and disorders characterized by behavioral dyscontrol over a rewarding behaviors (eating) shows that there is an over representation of abnormal activation (both to cues and during cognitive tasks) that frequently occur in areas where there is overlap between the ventral and the dorsal striatal pathways. This corroborates in humans that both the ventral striatum (predominantly associated with rewards processing) and the dorsal striatum (predominantly associated with habits and rituals in addiction) are disrupted in addictive disorders () and that these abnormalities influence processing of rewards (drugs and food) reward-associated stimuli (cues) and cognitive processes necessary for self-control (executive function). However medial temporal cortical regions that are part of the dorsal striatal pathway showed greater vulnerability to obesity and eating disorders than to drug addiction (Fig 4), indicating that there are also distinct pattern of abnormalities between these set of disorders.


Table 2 

Summary of functional neuroimaging studies (conducted between 2001 and 2011) on effects of cocaine addiction on brain function that were included in Figs 4 and ​and5.5. Studies are grouped by stimulation paradigm into five major categories. Number
Table 3 

Summary of fMRI studies (conducted between 2001 and 2011) on effects of methamphetamine addiction on brain function that were included in Figs 4 and ​and5.5. Studies are grouped by stimulation paradigm into two major categories. Number of methamphetamine


This work was accomplished with support from the National Institutes of Alcohol Abuse and Alcoholism (2RO1AA09481).



Declaration of interest

The authors report no declarations of interest.



  • Adcock R, Thangavel A, Whitfield-Gabrieli S, Knutson B, Gabrieli J. Reward-motivated learning: mesolimbic activation precedes memory formation. Neuron. 2006;50:507–517. [PubMed]
  • Asensio S, Romero M, Romero F, Wong C, Alia-Klein N, Tomasi D, Wang G, Telang F, Volkow N, Goldstein R. Striatal dopamine D2 receptor availability predicts the thalamic and medial prefrontal responses to reward in cocaine abusers three years later. Synapse. 2010;64:397–402. [PMC free article] [PubMed]
  • Atkinson T. Central and peripheral neuroendocrine peptides and signalling in appetite regulation: considerations for obesity pharmacotherapy. Obes Rev. 2008;9:108–120. [PubMed]
  • Avena N, Rada P, Hoebel B. Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev. 2008;32:20–39. [PMC free article] [PubMed]
  • Batterham R, ffytche D, Rosenthal J, Zelaya F, Barker G, Withers D, Williams S. PYY modulation of cortical and hypothalamic brain areas predicts feeding behaviour in humans. Nature. 2007;450:106–109. [PubMed]
  • Belin D, Everitt B. Cocaine seeking habits depend upon dopamine-dependent serial connectivity linking the ventral with the dorsal striatum. Neuron. 2008;57:432–441. [PubMed]
  • Biswal B, Mennes M, Zuo X, Gohel S, Kelly C, Smith S, Beckmann C, Adelstein J, Buckner R, Colcombe S, Dogonowski A, Ernst M, Fair D, Hampson M, Hoptman M, Hyde J, Kiviniemi V, Kötter R, Li S, Lin C, Lowe M, Mackay C, Madden D, Madsen K, Margulies D, Mayberg H, McMahon K, Monk C, Mostofsky S, Nagel B, Pekar J, Peltier S, Petersen S, Riedl V, Rombouts S, Rypma B, Schlaggar B, Schmidt S, Seidler R, Siegle GJ, Sorg C, Teng G, Veijola J, Villringer A, Walter M, Wang L, Weng X, Whitfield-Gabrieli S, Williamson P, Windischberger C, Zang Y, Zhang H, Castellanos F, Milham M. Toward discovery science of human brain function. Proc Natl Acad Sci U S A. 2010;107:4734–4739. [PMC free article] [PubMed]
  • Boileau I, Assaad J, Pihl R, Benkelfat C, Leyton M, Diksic M, Tremblay R, Dagher A. Alcohol promotes dopamine release in the human nucleus accumbens. Synapse. 2003;49:226–231. [PubMed]
  • Bolla K, Eldreth D, London E, Kiehl K, Mouratidis M, Contoreggi C, Matochik J, Kurian V, Cadet J, Kimes A, Funderburk F, Ernst M. Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a decision-making task. Neuroimage. 2003;19:1085–1094. [PMC free article] [PubMed]
  • Bolla K, Ernst M, Kiehl K, Mouratidis M, Eldreth D, Contoreggi C, Matochik J, Kurian V, Cadet J, Kimes A, Funderburk F, London E. Prefrontal cortical dysfunction in abstinent cocaine abusers. J Neuropsychiatry Clin Neurosci. 2004;16:456–464. [PMC free article] [PubMed]
  • Bossong M, van Berckel B, Boellaard R, Zuurman L, Schuit R, Windhorst A, van Gerven J, Ramsey N, Lammertsma A, Kahn R. Delta 9-tetrahydrocannabinol induces dopamine release in the human striatum. Neuropsychopharmacology. 2009;34:759–766. [PubMed]
  • Braskie M, Landau S, Wilcox C, Taylor S, O’Neil J, Baker S, Madison C, Jagust W. Correlations of striatal dopamine synthesis with default network deactivations during working memory in younger adults. Hum Brain Mapp. 2011;32:947–961. [PMC free article] [PubMed]
  • Brody A, Mandelkern M, Olmstead R, Allen-Martinez Z, Scheibal D, Abrams A, Costello M, Farahi J, Saxena S, Monterosso J, London E. Ventral striatal dopamine release in response to smoking a regular vs a denicotinized cigarette. Neuropsychopharmacology. 2009;32:282–289. [PMC free article] [PubMed]
  • Cannon C, Abdallah L, Tecott L, During M, Palmiter R. Dysregulation of striatal dopamine signaling by amphetamine inhibits feeding by hungry mice. Neuron. 2004;44:509–520. [PubMed]
  • Cason A, Smith R, Tahsili-Fahadan P, Moorman D, Sartor G, Aston-Jones G. Role of orexin/hypocretin in reward-seeking and addiction: implications for obesity. Physiol Behav. 2010;100:419–428. [PMC free article] [PubMed]
  • Chang L, Yakupov R, Cloak C, Ernst T. Marijuana use is associated with a reorganized visual-attention network and cerebellar hypoactivation. Brain. 2006;129:1096–1112. [PubMed]
  • Connolly C, Foxe J, Nierenberg J, Shpaner M, Garavan H. The neurobiology of cognitive control in successful cocaine abstinence. Drug Alcohol Depend. 2011 Epub ahead of print. [PMC free article] [PubMed]
  • Cota D, Tschop M, Horvath T, Levine A. Cannabinoids, opioids and eating behavior: the molecular face of hedonism? Brain Res Rev. 2006;51:85–107. [PubMed]
  • de Araujo I, Oliveira-Maia A, Sotnikova T, Gainetdinov R, Caron M, Nicolelis M, Simon S. Food reward in the absence of taste receptor signaling. Neuron. 2008;57:930–941. [PubMed]
  • Di Chiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci U S A. 1988;85:5274–5278. [PMC free article] [PubMed]
  • Di Martino A, Scheres A, Margulies D, Kelly A, Uddin L, Shehzad Z, Biswal B, Walters J, Castellanos F, Milham M. Functional connectivity of human striatum: a resting state FMRI study. Cereb Cortex. 2008;18:2735–2747. [PubMed]
  • Dimitropoulos A, Tkach J, Ho A, Kennedy J. Greater corticolimbic activation to high-calorie food cues after eating in obese vs. normal-weight adults. Appetite. 2012;58:303–312. [PMC free article] [PubMed]
  • Drevets W, Gautier C, Price J, Kupfer D, Kinahan P, Grace A, Price J, Mathis C. Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria. Biol Psychiatry. 2001;49:81–96. [PubMed]
  • Dunn J, Kessler R, Feurer I, Volkow N, Patterson B, Ansari M, Li R, Marks-Shulman P, Abumrad N. Relationship of dopamine type 2 receptor binding potential with fasting neuroendocrine hormones and insulin sensitivity in human obesity. Diabetes Care. 2012;35:1105–1111. [PMC free article] [PubMed]
  • Ersche K, Jones P, Williams G, Turton A, Robbins T, Bullmore E. Abnormal brain structure implicated in stimulant drug addiction. Science. 2012;335:601–604. [PubMed]
  • Everitt B, Belin D, Economidou D, Pelloux Y, Dalley J, Robbins T. Review. Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction. Philos Trans R Soc Lond B Biol Sci. 2008;363:3125–3135. [PMC free article] [PubMed]
  • Ferry A, Ongür D, An X, Price J. Prefrontal cortical projections to the striatum in macaque monkeys: evidence for an organization related to prefrontal networks. J Comp Neurol. 2000;425:447–470. [PubMed]
  • Filbey F, Claus E, Audette A, Niculescu M, Banich M, Tanabe J, Du Y, Hutchison K. Exposure to the taste of alcohol elicits activation of the mesocorticolimbic neurocircuitry. Neuropsychopharmacology. 2008;33:1391–1401. [PMC free article] [PubMed]
  • Filbey F, Schacht J, Myers U, Chavez R, Hutchison K. Marijuana craving in the brain. Proc Natl Acad Sci U S A. 2009;106:13016–13021. [PMC free article] [PubMed]
  • Fox M, Snyder A, Vincent J, Corbetta M, Van Essen D, Raichle M. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A. 2005;102:9673–9678. [PMC free article] [PubMed]
  • Frank G, Bailer U, Henry S, Drevets W, Meltzer C, Price J, Mathis C, Wagner A, Hoge J, Ziolko S, Barbarich-Marsteller N, Weissfeld L, Kaye W. Increased dopamine D2/D3 receptor binding after recovery from anorexia nervosa measured by positron emission tomography and [11c]raclopride. Biol Psychiatry. 2005;58:908–912. [PubMed]
  • Freund G, Ballinger WJ. Neuroreceptor changes in the putamen of alcohol abusers. Alcohol Clin Exp Res. 1989;13:213–218. [PubMed]
  • García-García I, Jurado M, Garolera M, Segura B, Sala-Llonch R, Marqués-Iturria I, Pueyo R, Sender-Palacios M, Vernet-Vernet M, Narberhaus A, Ariza M, Junqué C. Alterations of the salience network in obesity: A resting-state fMRI study. Hum Brain Mapp. 2012 doi: 10.1002/hbm.22104. [PubMed] [Cross Ref]
  • George M, Anton R, Bloomer C, Teneback C, Drobes D, Lorberbaum J, Nahas Z, Vincent D. Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues. Arch Gen Psychiatry. 2001;58:345–352. [PubMed]
  • Ghitza U, Preston K, Epstein D, Kuwabara H, Endres C, Bencherif B, Boyd S, Copersino M, Frost J, Gorelick D. Brain mu-opioid receptor binding predicts treatment outcome in cocaine-abusing outpatients. Biol Psychiatry. 2010;68:697–703. [PMC free article] [PubMed]
  • Gilman J, Ramchandani V, Crouss T, Hommer D. Subjective and neural responses to intravenous alcohol in young adults with light and heavy drinking patterns. Neuropsychopharmacology. 2012;37:467–477. [PMC free article] [PubMed]
  • Goldstein R, Alia-Klein N, Tomasi D, Carrillo J, Maloney T, Woicik P, Wang R, Telang F, Volkow N. Anterior cingulate cortex hypoactivations to an emotionally salient task in cocaine addiction. Proc Natl Acad Sci U S A. 2009a;106:9453–9458. [PMC free article] [PubMed]
  • Goldstein R, Alia-Klein N, Tomasi D, Zhang L, Cottone L, Maloney T, Telang F, Caparelli E, Chang L, Ernst T, Samaras D, Squires N, Volkow N. Is decreased prefrontal cortical sensitivity to monetary reward associated with impaired motivation and self-control in cocaine addiction? Am J Psychiatry. 2007a;164:1–9. [PMC free article] [PubMed]
  • Goldstein R, Tomasi D, Alia-Klein N, Carrillo J, Maloney T, Woicik P, Wang R, Telang F, Volkow N. Dopaminergic response to drug words in cocaine addiction. J Neurosci. 2009b;29:6001–6006. [PMC free article] [PubMed]
  • Goldstein R, Tomasi D, Rajaram S, Cottone L, Zhang L, Maloney T, Telang F, Alia-Klein N, Volkow N. Role of the anterior cingulate and medial orbitofrontal cortex in processing drug cues in cocaine addiction. Neuroscience. 2007b;144:1153–1159. [PMC free article] [PubMed]
  • Goldstein R, Volkow N. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry. 2002;159:1642–52. [PMC free article] [PubMed]
  • Goldstein R, Volkow N. Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nat Rev Neurosci. 2011;12:652–669. [PMC free article] [PubMed]
  • Goldstein R, Woicik P, Maloney T, Tomasi D, Alia-Klein N, Shan J, Honorio J, Samaras D, Wang R, Telang F, Wang G, Volkow N. Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task. Proc Natl Acad Sci U S A. 2010;107:16667–16672. [PMC free article] [PubMed]
  • Gorelick D, Kim Y, Bencherif B, Boyd S, Nelson R, Copersino M, Endres C, Dannals R, Frost J. Imaging brain mu-opioid receptors in abstinent cocaine users: time course and relation to cocaine craving. Biol Psychiatry. 2005;57:1573–1582. [PubMed]
  • Grace A. The tonic/phasic model of dopamine system regulation and its implications for understanding alcohol and psychostimulant craving. Addiction. 2000;95(Supp 2):S119–S128. [PubMed]
  • Grüsser S, Wrase J, Klein S, Hermann D, Smolka M, Ruf M, Weber-Fahr W, Flor H, Mann K, Braus D, Heinz A. Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics. Psychopharmacology (Berl) 2004;175:296–302. [PubMed]
  • Gu H, Salmeron B, Ross T, Geng X, Zhan W, Stein E, Yang Y. Mesocorticolimbic circuits are impaired in chronic cocaine users as demonstrated by resting-state functional connectivity. Neuroimage. 2010;53:593–601. [PMC free article] [PubMed]
  • Guan X, Yu H, Palyha O, McKee K, Feighner S, Sirinathsinghji D, Smith R, Van der Ploeg L, Howard A. Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res Mol Brain Res. 1997;48:23–29. [PubMed]
  • Gundersen H, Grüner R, Specht K, Hugdahl K. The effects of alcohol intoxication on neuronal activation at different levels of cognitive load. Open Neuroimag J. 2008;2:65–72. [PMC free article] [PubMed]
  • Haase L, Cerf-Ducastel B, Murphy C. Cortical activation in response to pure taste stimuli during the physiological states of hunger and satiety. Neuroimage. 2009;44:1008–1021. [PMC free article] [PubMed]
  • Haase L, Green E, Murphy C. Males and females show differential brain activation to taste when hungry and sated in gustatory and reward areas. Appetite. 2011;57:421–434. [PMC free article] [PubMed]
  • Haber S. The primate basal ganglia: parallel and integrative networks. J Chem Neuroanat. 2003;26:317–330. [PubMed]
  • Haber S, Fudge J, McFarland N. Striatonigrostriatal pathways in primates form an ascending spiral from the shell to the dorsolateral striatum. J Neurosci. 2000;20:2369–2382. [PubMed]
  • Haber S, Kim K, Mailly P, Calzavara R. Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning. J Neurosci. 2006;26:8368–8376. [PubMed]
  • Hanlon C, Wesley M, Stapleton J, Laurienti P, Porrino L. The association between frontal-striatal connectivity and sensorimotor control in cocaine users. Drug Alcohol Depend. 2011;115:240–243. [PMC free article] [PubMed]
  • Heitzeg M, Nigg J, Yau W, Zubieta J, Zucker R. Affective circuitry and risk for alcoholism in late adolescence: differences in frontostriatal responses between vulnerable and resilient children of alcoholic parents. Alcohol Clin Exp Res. 2008;32:414–426. [PMC free article] [PubMed]
  • Heitzeg M, Nigg J, Yau W, Zucker R, Zubieta J. Striatal dysfunction marks preexisting risk and medial prefrontal dysfunction is related to problem drinking in children of alcoholics. Biol Psychiatry. 2010;68:287–295. [PMC free article] [PubMed]
  • Hester R, Garavan H. Executive dysfunction in cocaine addiction: evidence for discordant frontal, cingulate, and cerebellar activity. J Neurosci. 2004;24:11017–11022. [PubMed]
  • Hester R, Garavan H. Neural mechanisms underlying drug-related cue distraction in active cocaine users. Pharmacol Biochem Behav. 2009;93:270–277. [PubMed]
  • Ikemoto S. Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory. Neurosci Biobehav Rev. 2010;35:129–150. [PMC free article] [PubMed]
  • Ilinsky I, Jouandet M, Goldman-Rakic P. Organization of the nigrothalamocortical system in the rhesus monkey. J Comp Neurol. 1985;236:315–330. [PubMed]
  • Johnson P, Kenny P. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 2010;13:635–641. [PMC free article] [PubMed]
  • Kalivas P. Glutamate systems in cocaine addiction. Curr Opin Pharmacol. 2004;4:23–29. [PubMed]
  • Kalivas P. The glutamate homeostasis hypothesis of addiction. Nat Rev Neurosci. 2009;10:561–572. [PubMed]
  • Kelly C, Zuo X, Gotimer K, Cox C, Lynch L, Brock D, Imperati D, Garavan H, Rotrosen J, Castellanos F, Milham M. Reduced interhemispheric resting state functional connectivity in cocaine addiction. Biol Psychiatry. 2011;69:684–692. [PMC free article] [PubMed]
  • Kelly R, Strick P. Macro-architecture of basal ganglia loops with the cerebral cortex: use of rabies virus to reveal multisynaptic circuits. Prog Brain Res. 2004;143 [PubMed]
  • King G, Ernst T, Deng W, Stenger A, Gonzales R, Nakama H, Chang L. Altered brain activation during visuomotor integration in chronic active cannabis users: relationship to cortisol levels. J Neurosci. 2011;31:17923–17931. [PMC free article] [PubMed]
  • Koob G. Neural mechanisms of drug reinforcement. Ann N Y Acad Sci. 1992;654:171–191. [PubMed]
  • Koob G, Le Moal M. Addiction and the brain antireward system. Annu Rev Psychol. 2008;59:29–53. [PubMed]
  • Kullmann S, Heni M, Veit R, Ketterer C, Schick F, Häring H, Fritsche A, Preissl H. The obese brain: association of body mass index and insulin sensitivity with resting state network functional connectivity. Hum Brain Mapp. 2012;33:1052–1061. [PubMed]
  • Künzle H. Bilateral projections from precentral motor cortex to the putamen and other parts of the basal ganglia. An autoradiographic study in Macaca fascicularis. Brain Res. 1975;88:195–209. [PubMed]
  • Künzle H. Projections from the primary somatosensory cortex to basal ganglia and thalamus in the monkey. Exp Brain Res. 1977;30:481–492. [PubMed]
  • Künzle H, Akert K. Efferent connections of cortical, area 8 (frontal eye field) in Macaca fascicularis. A reinvestigation using the autoradiographic technique. J Comp Neurol. 1977;173:147–164. [PubMed]
  • Lee B, London E, Poldrack R, Farahi J, Nacca A, Monterosso J, Mumford J, Bokarius A, Dahlbom M, Mukherjee J, Bilder R, Brody A, Mandelkern M. Striatal dopamine d2/d3 receptor availability is reduced in methamphetamine dependence and is linked to impulsivity. J Neurosci. 2009;29:14734–14740. [PMC free article] [PubMed]
  • Leland D, Arce E, Miller D, Paulus M. Anterior cingulate cortex and benefit of predictive cueing on response inhibition in stimulant dependent individuals. Biol Psychiatry. 2008;63:184–190. [PubMed]
  • Lenoir M, Serre F, Cantin L, Ahmed S. Intense sweetness surpasses cocaine reward. Plos One. 2007;2:e698. [PMC free article] [PubMed]
  • Li C, Huang C, Yan P, Bhagwagar Z, Milivojevic V, Sinha R. Neural correlates of impulse control during stop signal inhibition in cocaine-dependent men. Neuropsychopharmacology. 2008;33:1798–1806. [PMC free article] [PubMed]
  • Li C, Morgan P, Matuskey D, Abdelghany O, Luo X, Chang J, Rounsaville B, Ding Y, Malison R. Biological markers of the effects of intravenous methylphenidate on improving inhibitory control in cocaine-dependent patients. Proc Natl Acad Sci U S A. 2010;107:14455–14459. [PMC free article] [PubMed]
  • Liu J, Liang J, Qin W, Tian J, Yuan K, Bai L, Zhang Y, Wang W, Wang Y, Li Q, Zhao L, Lu L, von Deneen K, Liu Y, Gold M. Dysfunctional connectivity patterns in chronic heroin users: an fMRI study. Neurosci Lett. 2009;460:72–77. [PubMed]
  • Lock J, Garrett A, Beenhakker J, Reiss A. Aberrant brain activation during a response inhibition task in adolescent eating disorder subtypes. Am J Psychiatry. 2011;168:55–64. [PMC free article] [PubMed]
  • Lüscher C, Malenka R. Drug-evoked synaptic plasticity in addiction: from molecular changes to circuit remodeling. Neuron. 2011;69:650–663. [PMC free article] [PubMed]
  • Ma N, Liu Y, Fu X, Li N, Wang C, Zhang H, Qian R, Xu H, Hu X, Zhang D. Abnormal brain default-mode network functional connectivity in drug addicts. Plos One. 2011;6:e16560. [PMC free article] [PubMed]
  • Ma N, Liu Y, Li N, Wang C, Zhang H, Jiang X, Xu H, Fu X, Hu X, Zhang D. Addiction related alteration in resting-state brain connectivity. Neuroimage. 2010:738–744. [PMC free article] [PubMed]
  • Margulies D, Kelly A, Uddin L, Biswal B, Castellanos F, Milham M. Mapping the functional connectivity of anterior cingulate cortex. Neuroimage. 2007;37:579–588. [PubMed]
  • Middleton F, Strick P. Basal-ganglia ‘projections’ to the prefrontal cortex of the primate. Cereb Cortex. 2002;12:926–935. [PubMed]
  • Minzenberg M, Yoon J, Carter C. Modafinil modulation of the default mode network. Psychopharmacology (Berl) 2011;215:23–31. [PMC free article] [PubMed]
  • Moeller F, Steinberg J, Schmitz J, Ma L, Liu S, Kjome K, Rathnayaka N, Kramer L, Narayana P. Working memory fMRI activation in cocaine dependent subjects: Association with treatment response. Psych Res Neuroimaging. 2010;181:174–182. [PMC free article] [PubMed]
  • Norgren R, Hajnal A, Mungarndee S. Gustatory reward and the nucleus accumbens. Physiol Behav. 2006;89:531–535. [PMC free article] [PubMed]
  • Nummenmaa L, Hirvonen J, Hannukainen J, Immonen H, Lindroos M, Salminen P, Nuutila P. Dorsal striatum and its limbic connectivity mediate abnormal anticipatory reward processing in obesity. Plos One. 2012;7:e31089. [PMC free article] [PubMed]
  • Ogawa S, Lee TM, Kay AR, Tank DW. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Nat Acad Sci U S A. 1990;87:9868–9872. [PMC free article] [PubMed]
  • Padula C, Schweinsburg A, Tapert S. Spatial working memory performance and fMRI activation interaction in abstinent adolescent marijuana users. Psychol Addict Behav. 2007;21:478–487. [PMC free article] [PubMed]
  • Paulus M, Hozack N, Frank L, Brown G, Schuckit M. Decision making by methamphetamine-dependent subjects is associated with error-rate-independent decrease in prefrontal and parietal activation. Biol Psychiatry. 2003;53:65–74. [PubMed]
  • Paulus M, Hozack N, Zauscher B, Frank L, Brown G, Braff D, Schuckit M. Behavioral and functional neuroimaging evidence for prefrontal dysfunction in methamphetamine-dependent subjects. Neuropsychopharmacology. 2002;20:53–63. [PubMed]
  • Paulus M, Tapert S, Schuckit M. Neural activation patterns of methamphetamine-dependent subjects during decision making predict relapse. Arch Gen Psychiatry. 2005;62:761–768. [PubMed]
  • Phan K, Wager T, Taylor S, Liberzon I. Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. Neuroimage. 2002;16:331–348. [PubMed]
  • Postuma R, Dagher A. Basal ganglia functional connectivity based on a meta-analysis of 126 positron emission tomography and functional magnetic resonance imaging publications. Cereb Cortex. 2006;16:1508–1521. [PubMed]
  • Powell E, Leman R. Connections of the nucleus accumbens. Brain Res. 1976;105:389–403. [PubMed]
  • Rolls E. The orbitofrontal cortex and reward. Cereb Cortex. 2000;10:284–294. [PubMed]
  • Rothemund Y, Preuschhof C, Bohner G, Bauknecht H, Klingebiel R, Flor H, Klapp B. Differential activation of the dorsal striatum by high-calorie visual food stimuli in obese individuals. Neuroimage. 2007;37:410–421. [PubMed]
  • Rzepecki-Smith C, Meda S, Calhoun V, Stevens M, Jafri M, Astur R, Pearlson G. Disruptions in functional network connectivity during alcohol intoxicated driving. Alcohol Clin Exp Res. 2010;34:479–487. [PMC free article] [PubMed]
  • Salo R, Ursu S, Buonocore M, Leamon M, Carter C. Impaired Prefrontal Cortical Function and Disrupted Adaptive Cognitive Control in Methamphetamine Abusers: A Functional Magnetic Resonance Imaging Study. Biol Psychiatry 2009 [PMC free article] [PubMed]
  • Schienle A, Schäfer A, Hermann A, Vaitl D. Binge-eating disorder: reward sensitivity and brain activation to images of food. Biol Psychiatry. 2009;65:654–661. [PubMed]
  • Selemon L, Goldman-Rakic P. Longitudinal topography and interdigitation of corticostriatal projections in the rhesus monkey. J Neurosci. 1985;5:776–794. [PubMed]
  • Silveri M, Rogowska J, McCaffrey A, Yurgelun-Todd D. Adolescents At Risk for Alcohol Abuse Demonstrate Altered Frontal Lobe Activation During Stroop Performance. Alcohol Clin Exp Res. 2011;35:218–228. [PMC free article] [PubMed]
  • Sotak B, Hnasko T, Robinson S, Kremer E, Palmiter R. Dysregulation of dopamine signaling in the dorsal striatum inhibits feeding. Brain Res. 2005;1061:88–96. [PubMed]
  • Stice E, Spoor S, Bohon C, Small D. Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science. 2008;322:449–452. [PMC free article] [PubMed]
  • Stice E, Yokum S, Burger K, Epstein L, Small D. Youth at risk for obesity show greater activation of striatal and somatosensory regions to food. J Neurosci. 2011;31:4360–4366. [PMC free article] [PubMed]
  • Stoeckel L, Weller R, Cook Er, Twieg D, Knowlton R, Cox J. Widespread reward-system activation in obese women in response to pictures of high-calorie foods. Neuroimage. 2008;41:636–647. [PubMed]
  • Stokes P, Egerton A, Watson B, Reid A, Lappin J, Howes O, Nutt D, Lingford-Hughes A. History of cannabis use is not associated with alterations in striatal dopamine D2/D3 receptor availability. J Psychopharmacol. 2012;26:144–149. [PubMed]
  • Tapert S, Schweinsburg A, Drummond S, Paulus M, Brown S, Yang T, Frank L. Functional MRI of inhibitory processing in abstinent adolescent marijuana users. Psychopharmacology (Berl) 2007;194:173–183. [PMC free article] [PubMed]
  • Tomasi D, Ernst T, Caparelli E, Chang L. Common deactivation patterns during working memory and visual attention tasks: An intra-subject fMRI study at 4 Tesla. Hum Brain Mapp. 2006;27:694–705. [PMC free article] [PubMed]
  • Tomasi D, Goldstein R, Telang F, Maloney T, Alia-Klein N, Caparelli E, Volkow N. Cocaine abusers have widespread disruption in brain activation patterns to a working memory task. Brain Res. 2007a;1171:83–92. [PMC free article] [PubMed]
  • Tomasi D, Goldstein R, Telang F, Maloney T, Alia-Klein N, Caparelli E, Volkow N. Thalamocortical dysfunction in cocaine abusers: implications in attention and perception. Psych Res Neuroimaging. 2007b;155:189–201. [PMC free article] [PubMed]
  • Tomasi D, Volkow N. Association between Functional Connectivity Hubs and Brain Networks. Cereb Cortex. 2011;21:2003–2013. [PMC free article] [PubMed]
  • Tomasi D, Volkow N, Wang G, Wang R, Telang F, Caparelli E, Wong C, Jayne M, Fowler J. Methylphenidate enhances brain activation and deactivation responses to visual attention and working memory tasks in healthy controls. Neuroimage. 2011;54:3101–3110. [PMC free article] [PubMed]
  • Tomasi D, Volkow N, Wang R, Carrillo J, Maloney T, Alia-Klein N, Woicik P, Telang F, Goldstein R. Disrupted functional connectivity with dopaminergic midbrain in cocaine abusers. Plos One. 2010;5:e10815. [PMC free article] [PubMed]
  • Tomasi D, Volkow N, Wang R, Telang F, Wang G, Chang L, Ernst T, Fowler J. Dopamine Transporters in Striatum Correlate with Deactivation in the Default Mode Network during Visuospatial Attention. PLoS ONE. 2009a;4:e6102. [PMC free article] [PubMed]
  • Tomasi D, Wang G, Wang R, Backus W, Geliebter A, Telang F, Jayne M, Wong C, Fowler J, Volkow N. Association of body mass and brain activation during gastric distention: implications for obesity. PLoS ONE. 2009b;4:e6847. [PMC free article] [PubMed]
  • Upadhyay J, Maleki N, Potter J, Elman I, Rudrauf D, Knudsen J, Wallin D, Pendse G, McDonald L, Griffin M, Anderson J, Nutile L, Renshaw P, Weiss R, Becerra L, Borsook D. Alterations in brain structure and functional connectivity in prescription opioid-dependent patients. Brain. 2010;133:2098–2114. [PMC free article] [PubMed]
  • Urban N, Slifstein M, Thompson J, Xu X, Girgis R, Raheja S, Haney M, Abi-Dargham A. Dopamine release in chronic cannabis users: a [(11)c]raclopride positron emission tomography study. Biol Psychiatry. 2012;71:677–683. [PMC free article] [PubMed]
  • Volkow N, Baler R. Neuroscience. To stop or not to stop? Science. 2012;335:546–548. [PMC free article] [PubMed]
  • Volkow N, Chang L, Wang G, Fowler J, Ding Y, Sedler M, Logan J, Franceschi D, Gatley J, Hitzemann R, Gifford A, Wong C, Pappas N. Low level of brain dopamine d(2) receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex. Am J Psychiatry. 2001a;158:2015–2021. [PubMed]
  • Volkow N, Chang L, Wang G-J, Fowler J, Franceschi D, Sedler M, Gatley S, Miller E, Hitzemann R, Ding Y-S, Logan J. Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence. J Neurosci. 2001b;21:9414–9418. [PubMed]
  • Volkow N, Ding Y, Fowler J, Wang G. Cocaine addiction: hypothesis derived from imaging studies with PET. J Addict Dis. 1996a;15:55–71. [PubMed]
  • Volkow N, Fowler J. Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cereb Cortex. 2000;10:318–325. [PubMed]
  • Volkow N, Fowler J, Wang G. The addicted human brain: insights from imaging studies. J Clin Invest. 2003a;111:1444–1451. [PMC free article] [PubMed]
  • Volkow N, Fowler J, Wang G, Telang F, Logan J, Jayne M, Ma Y, Pradhan K, Wong C, Swanson J. Cognitive control of drug craving inhibits brain reward regions in cocaine abusers. Neuroimage. 2010a;49:2536–2543. [PMC free article] [PubMed]
  • Volkow N, Gillespie H, Mullani N, Tancredi L, Grant C, Valentine A, Hollister L. Brain glucose metabolism in chronic marijuana users at baseline and during marijuana intoxication. Psychiatry Res. 1996b;67:29–38. [PubMed]
  • Volkow N, Li T. The neuroscience of addiction. Nat Neurosci. 2005;8:1429–1430. [PubMed]
  • Volkow N, Tomasi D, Wang G, Fowler J, Telang F, Goldstein R, Alia-Klein N, Wong C. Reduced metabolism in brain “control networks” following cocaine-cues exposure in female cocaine abusers. PLoS One. 2011a;6:e16573. [PMC free article] [PubMed]
  • Volkow N, Wang G, Baler R. Reward, dopamine and the control of food intake: implications for obesity. Trends Cogn Sci. 2011b;15:37–46. [PMC free article] [PubMed]
  • Volkow N, Wang G, Begleiter H, Porjesz B, Fowler J, Telang F, Wong C, Ma Y, Logan J, Goldstein R, Alexoff D, Thanos P. High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors. Arch Gen Psychiatry. 2006;63:999–1008. [PubMed]
  • Volkow N, Wang G, Fowler J, Logan J, Gatley S, Hitzemann R, Chen A, Dewey S, Pappas N. Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects. Nature. 1997a;386:830–833. [PubMed]
  • Volkow N, Wang G, Fowler J, Logan J, Gatley S, MacGregor R, Schlyer D, Hitzemann R, Wolf A. Measuring age-related changes in dopamine D2 receptors with 11C-raclopride and 18F-N-methylspiroperidol. Psychiatry Res. 1996c;67:11–16. [PubMed]
  • Volkow N, Wang G, Fowler J, Logan J, Gatley S, Wong C, Hitzemann R, Pappas N. Reinforcing effects of psychostimulants in humans are associated with increases in brain dopamine and occupancy of D(2) receptors. J Pharmacol Exp Ther. 1999;291:409–415. [PubMed]
  • Volkow N, Wang G, Fowler J, Logan J, Jayne M, Franceschi D, Wong C, Gatley S, Gifford A, Ding Y, Pappas N. “Nonhedonic” food motivation in humans involves dopamine in the dorsal striatum and methylphenidate amplifies this effect. Synapse. 2002;44:175–180. [PubMed]
  • Volkow N, Wang G, Fowler J, Telang F. Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology. Philos Trans R Soc Lond B Biol Sci. 2008a;363:3191–3200. [PMC free article] [PubMed]
  • Volkow N, Wang G, Fowler J, Tomasi D. Addiction circuitry in the human brain. Annu Rev Pharmacol Toxicol. 2012a;52:321–336. [PMC free article] [PubMed]
  • Volkow N, Wang G, Fowler J, Tomasi D, Baler R. Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction. Curr Top Behav Neurosci. 2012b doi: 10.1007/7854_2011_169. Epub ahead of print. [PubMed] [Cross Ref]
  • Volkow N, Wang G, Fowler J, Tomasi D, Telang F. Addiction: beyond dopamine reward circuitry. Proc Natl Acad Sci U S A. 2011c;108:15037–15042. [PMC free article] [PubMed]
  • Volkow N, Wang G, Ma Y, Fowler J, Wong C, Ding Y, Hitzemann R, Swanson J, Kalivas P. Activation of orbital and medial prefrontal cortex by methylphenidate in cocaine-addicted subjects but not in controls: relevance to addiction. J Neurosci. 1995;25:3932–3939. [PubMed]
  • Volkow N, Wang G, Maynard L, Jayne M, Fowler J, Zhu W, Logan J, Gatley S, Ding Y, Wong C, Pappas N. Brain dopamine is associated with eating behaviors in humans. Int J Eat Disord. 2003b;33:136–142. [PubMed]
  • Volkow N, Wang G, Telang F, Fowler J, Logan J, Jayne M, Ma Y, Pradhan K, Wong C. Profound decreases in dopamine release in striatum in detoxified alcoholics: possible orbitofrontal involvement. J Neurosci. 2007;27:12700–12706. [PubMed]
  • Volkow N, Wang G, Telang F, Fowler J, Thanos P, Logan J, Alexoff D, Ding Y, Wong C, Ma Y, Pradhan K. Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors. Neuroimage. 2008b;42:1537–1543. [PMC free article] [PubMed]
  • Volkow N, Wang G, Tomasi D, Telang F, Fowler J, Pradhan K, Jayne M, Logan J, Goldstein R, Alia-Klein N, Wong C. Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers. PLoS ONE. 2010b;5:e11509. [PMC free article] [PubMed]
  • Volkow ND, Fowler JS, Wang GJ, Hitzemann R, Logan J, Schlyer DJ, Dewey SL, Wolf AP. Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers. Synapse. 1993;14:169–177. [PubMed]
  • Volkow ND, Wang GJ, Fischman MW, Foltin RW, Fowler JS, Abumrad NN, Vitkun S, Logan J, Gatley SJ, Pappas N, Hitzemann R, Shea CE. Relationship between subjective effects of cocaine and dopamine transporter occupancy. Nature. 1997b;386:827–830. [PubMed]
  • Vollstädt-Klein S, Hermann D, Rabinstein J, Wichert S, Klein O, Ende G, Mann K. Increased activation of the ACC during a spatial working memory task in alcohol-dependence versus heavy social drinking. Alcohol Clin Exp Res. 2010a;34:771–776. [PubMed]
  • Vollstädt-Klein S, Wichert S, Rabinstein J, Bühler M, Klein O, Ende G, Hermann D, Mann K. Initial, habitual and compulsive alcohol use is characterized by a shift of cue processing from ventral to dorsal striatum. Addiction. 2010b;105:1741–1749. [PubMed]
  • Wager T, Jonides J, Reading S. Neuroimaging studies of shifting attention: a meta-analysis. Neuroimage. 2004;22:1679–1693. [PubMed]
  • Wallner-Liebmann S, Koschutnig K, Reishofer G, Sorantin E, Blaschitz B, Kruschitz R, Unterrainer H, Gasser R, Freytag F, Bauer-Denk C, Schienle A, Schäfer A, Mangge H. Insulin and hippocampus activation in response to images of high-calorie food in normal weight and obese adolescents. Obesity. 2010;18:1552–1557. [PubMed]
  • Wanat M, Willuhn I, Clark J, Phillips P. Phasic dopamine release in appetitive behaviors and drug addiction. Curr Drug Abuse Rev. 2009;2:195–213. [PMC free article] [PubMed]
  • Wang G, Geliebter A, Volkow N, Telang F, Logan J, Jayne M, Galanti K, Selig P, Han H, Zhu W, Wong C, Fowler J. Enhanced striatal dopamine release during food stimulation in binge eating disorder. Obesity. 2011a;19:1601–1608. [PMC free article] [PubMed]
  • Wang G, Smith L, Volkow N, Telang F, Logan J, Tomasi D, Wong C, Hoffman W, Jayne M, Alia-Klein N, Thanos P, Fowler J. Decreased dopamine activity predicts relapse in methamphetamine abusers. Mol Psychiatry. 2011b doi: 10.1038/mp.2011.86. [PMC free article] [PubMed] [Cross Ref]
  • Wang G, Volkow N, Chang L, Miller E, Sedler M, Hitzemann R, Zhu W, Logan J, Ma Y, Fowler J. Partial recovery of brain metabolism in methamphetamine abusers after protracted abstinence. Am J Psychiatry. 2004;161:242–248. [PubMed]
  • Wang G, Volkow N, Logan J, Pappas N, Wong C, Zhu W, Netusil N, Fowler J. Brain dopamine and obesity. Lancet. 2001;357:354–357. [PubMed]
  • Wang G, Volkow N, Telang F, Jayne M, Ma Y, Pradhan K, Zhu W, Wong C, Thanos P, Geliebter A, Biegon A, Fowler J. Evidence of gender differences in the ability to inhibit brain activation elicited by food stimulation. Proc Natl Acad Sci U S A. 2009;106:1249–1254. [PMC free article] [PubMed]
  • Wilcox C, Teshiba T, Merideth F, Ling J, Mayer A. Enhanced cue reactivity and fronto-striatal functional connectivity in cocaine use disorders. Drug Alcohol Depend. 2011;115:137–144. [PMC free article] [PubMed]
  • Wilczak N, De Bleser P, Luiten P, Geerts A, Teelken A, De Keyser J. Insulin-like growth factor II receptors in human brain and their absence in astrogliotic plaques in multiple sclerosis. Brain Res. 2000;863:282–288. [PubMed]
  • Williams L, Adam C, Mercer J, Moar K, Slater D, Hunter L, Findlay P, Hoggard N. Leptin receptor and neuropeptide Y gene expression in the sheep brain. J Neuroendocrinol. 1999;11:165–169. [PubMed]
  • Wise R. Roles for nigrostriatal–not just mesocorticolimbic–dopamine in reward and addiction. Trends Neurosci. 2009;32:517–524. [PMC free article] [PubMed]
  • Wittmann B, Schott B, Guderian S, Frey J, Heinze H, Düzel E. Reward-related FMRI activation of dopaminergic midbrain is associated with enhanced hippocampus-dependent long-term memory formation. Neuron. 2005;45:459–467. [PubMed]
  • Wrase J, Schlagenhauf F, Kienast T, Wüstenberg T, Bermpohl F, Kahnt T, Beck A, Ströhle A, Juckel G, Knutson B, Heinz A. Dysfunction of reward processing correlates with alcohol craving in detoxified alcoholics. Neuroimage. 2007;35:787–794. [PubMed]
  • Yeterian E, Van Hoesen G. Cortico-striate projections in the rhesus monkey: the organization of certain cortico-caudate connections. Brain Res. 1978;139:43–63. [PubMed]
  • Yoon H, Chung J, Oh J, Min H, Kim D, Cheon Y, Joe K, Kim Y, Cho Z. Differential activation of face memory encoding tasks in alcohol-dependent patients compared to healthy subjects: an fMRI study. Neurosci Lett. 2009;450:311–316. [PubMed]
  • Zweifel L, Parker J, Lobb C, Rainwater A, Wall V, Fadok J, Darvas M, Kim M, Mizumori S, Paladini C, Phillips P, Palmiter R. Disruption of NMDAR-dependent burst firing by dopamine neurons provides selective assessment of phasic dopamine-dependent behavior. Proc Natl Acad Sci U S A. 2009;106:7281–7288. [PMC free article] [PubMed]