NMR-based Metabolomics and Fatty Acid Profiles to Unravel Biomarkers in Preclinical Animal Models of Compulsive Behavior.

Compulsivity is a key manifestation of inhibitory control deficit and a cardinal symptom of psychopathological conditions such as obsessive-compulsive and attention-deficit hyperactivity disorders, in which metabolic alterations have raised attention as putative biomarkers for early identification. The present study assessed the metabolic profile in a preclinical model of a compulsive phenotype of rats. We used the schedule-induced polydipsia (SIP) method to classify male Wistar rats into high drinkers (HDs) or low drinkers (LDs) according to their compulsive drinking rate developed by exposure to a fixed-time 60 s (FT-60) schedule of reinforcement with water available ad libitum during 20 sessions. Before and after SIP, blood samples were collected for subsequent serum analysis by nuclear magnetic resonance spectroscopy coupled to multivariate analysis. Although no differences existed in the pre-SIP set, the compulsive drinking behavior induced remarkable metabolic alterations: HD rats selected by SIP exhibited a hyperlipidemic, hypoglycemic, and hyperglutaminergic profile compared with their low-compulsive counterparts. Interestingly, these alterations were not attributable to the mere exposure to reward pellets because a control experiment did not show differences between HDs and LDs after 20 sessions of pellet consumption without intermittent reinforcement. Our results shed light toward the implication of dietary and metabolic factors underpinning the vulnerability to compulsive behaviors.

Increased amygdala and decreased hippocampus volume after schedule-induced polydipsia in high drinker compulsive rats.

Fronto-limbic structures and serotonin 2A receptors (5-HT2A) have been implicated in the pathophysiology and treatment of compulsive spectrum disorders. Schedule-Induced Polydipsia (SIP), characterized by the development of excessive drinking under intermittent food reinforcement schedules, is a valid preclinical model for studying the compulsive phenotype. In the present study, we explored the individual differences and effect of SIP in brain volume and 5-HT2A receptor binding in fronto-limbic structures in rats selected according to their compulsive drinking behavior. Rats were divided into high (HD) and low drinkers (LD) by SIP (20 sessions); later, we analyzed the brains of HD and LD selected rats, in two different conditions: non-re-exposure (NRE) or re-exposure to SIP (RE), with four groups: LD-NRE, LD-RE, HD-NRE and HD-RE. Histological analyses were carried out for volumetric (stereology) and receptor binding (autoradiography) in the prelimbic and infralimbic cortex, dorsal hippocampus and basolateral amygdala. After SIP re-exposure, HD-RE showed an increased basolateral amygdala and a reduced hippocampus volume compared to HD-NRE rats, and also compared to LD-RE rats. No differences were found between HD and LD in NRE condition. Moreover, HD rats exhibit a lower 5-HT2A receptor binding in the basolateral amygdala, independently of SIP re-exposure, compared to LD rats. However, LD-RE showed a decreased 5-HT2A receptor binding in basolateral amygdala compared to LD-NRE. No differences were found in the remaining structures. These findings suggest that SIP might be differentially impacting HD and LD brains, pointing towards a possible explanation of how the latent vulnerability to compulsivity is triggered.

Neuroendocrinological mechanisms underlying impulsive and compulsive behaviors in obesity: a narrative review of fMRI studies.

Impulsivity and compulsivity are multidimensional constructs that are increasingly considered determinants of obesity. Studies using functional magnetic resonance imaging (fMRI) have provided insight on how differences in brain response during tasks exploring facets of impulsivity and compulsivity relate to the ingestive behaviors that support the etiology and maintenance of obesity. In this narrative review, we provide an overview of neuroimaging studies exploring impulsivity and compulsivity factors as they relate to weight status. Special focus will be placed on studies examining the impulsivity-related dimensions of attentional bias, delayed gratification and emotion regulation. Discussions of compulsivity within the context of obesity will be restricted to fMRI studies investigating habit formation and response flexibility under shifting contingencies. Further, we will highlight neuroimaging research demonstrating how alterations in neuroendocrine functioning are linked to excessive food intake and may serve as a driver of the impulsive and compulsive behaviors observed in obesity. Research on the associations between brain response with neuroendocrine factors, such as insulin, peptide YY (PYY), leptin, ghrelin and glucagon-like peptide 1 (GLP-1), will be reviewed.

Lower nucleus accumbens α-synuclein load and D3 receptor levels in Parkinson's disease with impulsive compulsive behaviours.

Impulsive compulsive behaviours in Parkinson's disease have been linked to increased dopaminergic release in the ventral striatum and excessive stimulation of dopamine D3 receptors. Thirty-one patients with impulsive compulsive behaviours and Parkinson's disease who donated their brains to the Queen Square Brain Bank for Neurological Disorders were assessed for α-synuclein neuropathological load and tyrosine hydroxylase levels in the nucleus accumbens, dorsal putamen and caudate using immunohistochemistry. Dopamine D2 and dopamine D3 receptors protein levels in the nucleus accumbens, frontal cortex and putamen were determined using western blotting. Results were compared to 29 Parkinson's disease cases without impulsive compulsive behaviours matched by age, sex, disease duration, age at Parkinson's disease onset and disease duration. The majority of patients with impulsive compulsive behaviours had dopamine dysregulation syndrome. Patients with Parkinson's disease and impulsive compulsive behaviours had lower α-synuclein load and dopamine D3 receptor levels in the nucleus accumbens. No differences were seen between groups in the other brain areas and in the analysis of tyrosine hydroxylase and dopamine D2 receptor levels. Lower α-synuclein load in the nucleus accumbens of individuals with Parkinson's disease and impulsive compulsive behaviours was confirmed on western blotting. Downregulation of the dopamine D3 receptor levels may have occurred either as a consequence of the degenerative process or of a pre-morbid trait. The lower levels of α-synuclein may have contributed to an excessive stimulation of the ventral striatum resulting in impulsive compulsive behaviours.

Amelioration of obsessive-compulsive disorder in three mouse models treated with one epigenetic drug: unraveling the underlying mechanism.

Mental health disorders are manifested in families, yet cannot be fully explained by classical Mendelian genetics. Changes in gene expression via epigenetics present a plausible mechanism. Anxiety often leads to avoidant behaviors which upon repetition may become habitual, maladaptive and resistant to extinction as observed in obsessive compulsive disorders (OCD). Psychophysical models of OCD propose that anxiety (amygdala) and habits (dorsolateral striatum, DLS) may be causally linked. The amygdala activates spiny projection neurons in the DLS. Repetitive amygdala terminal stimulation in the DLS elicits long term OCD-like behavior in mice associated with circuitry changes and gene methylation-mediated decrease in the activity of protein phosphatase 1 (PP1). Treatment of OCD-like grooming behavior in Slitrk5, SAPAP3, and laser-stimulated mice with one dose of RG108 (DNA methyltransferase inhibitor), lead to marked symptom improvement lasting for at least one week as well as complete reversal of anomalous changes in circuitry and PP1 gene methylation.

Compulsivity and impulsivity traits linked to attenuated developmental frontostriatal myelination trajectories.

The transition from adolescence to adulthood is a period when ongoing brain development coincides with a substantially increased risk of psychiatric disorders. The developmental brain changes accounting for this emergent psychiatric symptomatology remain obscure. Capitalizing on a unique longitudinal dataset that includes in vivo myelin-sensitive magnetization transfer (MT) MRI scans, we show that this developmental period is characterized by brain-wide growth in MT trajectories within both gray matter and adjacent juxtacortical white matter. In this healthy population, the expression of common developmental traits, namely compulsivity and impulsivity, is tied to a reduced growth of these MT trajectories in frontostriatal regions. This reduction is most marked in dorsomedial and dorsolateral prefrontal regions for compulsivity and in lateral and medial prefrontal regions for impulsivity. These findings highlight that psychiatric traits of compulsivity and impulsivity are linked to regionally specific reductions in myelin-related growth in late adolescent brain development.

Stochastic synaptic plasticity underlying compulsion in a model of addiction.

Activation of the mesolimbic dopamine system reinforces goal-directed behaviours. With repetitive stimulation-for example, by chronic drug abuse-the reinforcement may become compulsive and intake continues even in the face of major negative consequences. Here we gave mice the opportunity to optogenetically self-stimulate dopaminergic neurons and observed that only a fraction of mice persevered if they had to endure an electric shock. Compulsive lever pressing was associated with an activity peak in the projection terminals from the orbitofrontal cortex (OFC) to the dorsal striatum. Although brief inhibition of OFC neurons temporarily relieved compulsive reinforcement, we found that transmission from the OFC to the striatum was permanently potentiated in persevering mice. To establish causality, we potentiated these synapses in vivo in mice that stopped optogenetic self-stimulation of dopamine neurons because of punishment; this led to compulsive lever pressing, whereas depotentiation in persevering mice had the converse effect. In summary, synaptic potentiation of transmission from the OFC to the dorsal striatum drives compulsive reinforcement, a defining symptom of addiction.

Activation of cortical and striatal regions during the expression of a naturalistic compulsive-like behavior in the rabbit.

Nest building behavior in the pregnant rabbit (Oryctolagus cuniculus) can serve as a model for compulsions in obsessive compulsive disorder (OCD). Previous work showed that the "straw carrying" phase of nest building (during which the rabbit repeatedly collects straw in its mouth, carries it into the nest box and deposits it there, and then returns to collect more) is associated with increased c-FOS expression (a marker of neuronal activity) in the orbitofrontal, anterior cingulate, and piriform cortices. In the present study, we quantified c-FOS expression in the caudate and putamen, as well as in the primary motor, somatosensory, and prefrontal cortices of: (1) pregnant rabbits given straw (PREG + STRAW); pregnant rabbits not given straw (PREG); (3) estrous rabbits given straw (ESTROUS + STRAW); and (4) estrous rabbits not given straw (ESTROUS). We found that straw carrying was associated with increased c-FOS expression in the dorsal putamen, ventral caudate, primary motor cortex, and somatosensory cortex. Additionally, a correlational analysis of PREG + STRAW animals revealed that these regions, along with the premotor and prelimbic cortices, were significantly intercorrelated with respect to c-FOS expression, suggesting their "coactivation" during repetitive straw carrying. By contrast, behavioral interactions of non-pregnant (ESTROUS) rabbits with straw (e.g., sniffing, nibbling it) were associated with a distinct pattern of c-FOS expression that included the medial and ventral putamen. c-FOS expression in PREG + STRAW rabbits is similar to patterns of regional brain activity in OCD patients exposed to obsession-provoking stimuli, as well as to those observed in healthy human mothers responding to infant-associated stimuli.

Median and Dorsal Raphe Serotonergic Neurons Control Moderate Versus Compulsive Cocaine Intake.

BACKGROUND: Reduced expression of the serotonin transporter (SERT) promotes anxiety and cocaine intake in both humans and rats. We tested the hypothesis that median raphe nucleus (MRN) and dorsal raphe nucleus (DRN) serotonergic projections differentially mediate these phenotypes. METHODS: We used virally mediated RNA interference to locally downregulate SERT expression and compared the results with those of constitutive SERT knockout. Rats were allowed either short access (ShA) (1 hour) or long access (LgA) (6 hours) to cocaine self-administration to model moderate versus compulsive-like cocaine taking. RESULTS: SERT knockdown in the MRN increased cocaine intake selectively under ShA conditions and, like ShA cocaine self-administration, reduced corticotropin-releasing factor (CRF) immunodensity in the paraventricular nucleus of the hypothalamus. In contrast, SERT knockdown in the DRN increased cocaine intake selectively under LgA conditions and, like LgA cocaine self-administration, reduced CRF immunodensity in the central nucleus of the amygdala. SERT knockdown in the MRN or DRN produced anxiety-like behavior, as did withdrawal from ShA or LgA cocaine self-administration. The phenotype of SERT knockout rats was a summation of the phenotypes generated by MRN- and DRN-specific SERT knockdown. CONCLUSIONS: Our results highlight a differential role of serotonergic projections arising from the MRN and DRN in the regulation of cocaine intake. We propose that a cocaine-induced shift from MRN-driven serotonergic control of CRF levels in the hypothalamus to DRN-driven serotonergic control of CRF levels in the amygdala may contribute to the transition from moderate to compulsive intake of cocaine.

Can we predict development of impulsive-compulsive behaviours in Parkinson's disease?

OBJECTIVE: To determine clinical and structural imaging predictors of impulsive-compulsive behaviour (ICB) in de novo Parkinson's disease (PD). METHODS: From a cohort of 1116 subjects from the Parkinson's Progression Marker Initiative database, we created a subcohort of 42 de novo PD without ICB at baseline with available 3T MRI and who developed ICB during follow-up. PD-ICB were matched for age, gender and disease duration to 42 patients with PD without ICB over follow-up (PD-no-ICB) and 42 healthy controls (HCs). Baseline demographic and clinical predictors of ICB were analysed. For the longitudinal neuroimaging analysis, we selected 27 patients with PD-ICB with available neuroimaging after ICB onset, who were matched with 32 PD-no-ICB and 35 HCs. Baseline and longitudinal structural differences were compared using voxel-based morphometry and voxel-based quantification. RESULTS: People who went on to develop ICB had more severe anxiety, worse autonomic and global cognitive functions and were more likely to have rapid eye movement sleep behaviour disorder. Logistic regression confirmed that worse autonomic and cognitive functions were predictors of ICB. We could not find any morphological feature on baseline MRI that predicted later onset of ICB. When comparing PD groups at follow-up, a small region of increased atrophy in the anterior limb of the left internal capsule adjacent to the head of the left caudate nucleus was found in PD-ICB, but not surviving correction for multiple comparisons. CONCLUSIONS: Worse autonomic and cognitive functions predict development of ICB at the time of PD diagnosis. Structural imaging fails to identify morphological features associated with the development of ICB.

Dependence-induced increase of alcohol self-administration and compulsive drinking mediated by the histone methyltransferase PRDM2.

Epigenetic processes have been implicated in the pathophysiology of alcohol dependence, but the specific molecular mechanisms mediating dependence-induced neuroadaptations remain largely unknown. Here, we found that a history of alcohol dependence persistently decreased the expression of Prdm2, a histone methyltransferase that monomethylates histone 3 at the lysine 9 residue (H3K9me1), in the rat dorsomedial prefrontal cortex (dmPFC). Downregulation of Prdm2 was associated with decreased H3K9me1, supporting that changes in Prdm2 mRNA levels affected its activity. Chromatin immunoprecipitation followed by massively parallel DNA sequencing showed that genes involved in synaptic communication are epigenetically regulated by H3K9me1 in dependent rats. In non-dependent rats, viral-vector-mediated knockdown of Prdm2 in the dmPFC resulted in expression changes similar to those observed following a history of alcohol dependence. Prdm2 knockdown resulted in increased alcohol self-administration, increased aversion-resistant alcohol intake and enhanced stress-induced relapse to alcohol seeking, a phenocopy of postdependent rats. Collectively, these results identify a novel epigenetic mechanism that contributes to the development of alcohol-seeking behavior following a history of dependence.

Activation of the orbitofrontal and anterior cingulate cortices during the expression of a naturalistic compulsive-like behavior in the rabbit.

We propose that maternal nest building in the female laboratory rabbit is a useful model for compulsions in obsessive-compulsive disorder (OCD). This repetitive behavior comprises collecting straw, depositing it into the nest box, and then returning to collect more straw. We reasoned that if "straw carrying" behavior is homologous to compulsive behavior, then it should be associated with activation of prefrontal regions associated with OCD, namely, the orbitofrontal and anterior cingulate cortices (OFC and ACC, respectively). In the present study, we quantified c-FOS immunoreactivity in the ACC, OFC, premotor (PM), infralimbic (IL), prelimbic (PL), and piriform (PI) cortices of: (1) pregnant female rabbits that were given straw (PREG+STRAW); (2) pregnant rabbits that were not given straw (PREG); (3) estrous rabbits that were given straw (ESTROUS+STRAW); (4) estrous rabbits that were not given straw (ESTROUS). After 1h, all females were sacrificed and processed for brain c-FOS immunoreactivity. We found that pregnant rabbits showed lower latencies to interact with the straw than estrous rabbits, and that pregnant rabbits displayed straw carrying, while estrous rabbits did not. c-FOS expression was increased in the OFC, ACC, and PI in the PREG+STRAW compared to all other groups. By contrast, c-FOS expression in all other regions was greater in PREG+STRAW compared to PREG, but not different from ESTROUS+STRAW. These results point to an important role for the OFC, ACC, and PI in initiating repetitive straw-carrying behavior, and further support the proposal that this behavior can serve as a model for compulsions in OCD.

Behavioral Biomarkers of Schizophrenia in High Drinker Rats: A Potential Endophenotype of Compulsive Neuropsychiatric Disorders.

Psychogenic polydipsia, which is compulsive, non-regulatory fluid consumption, is present in 6%-20% of chronic psychiatric patients and frequently associated with the schizophrenia diagnosis. In the present study, we investigated the relation between schizophrenia-like symptoms and biomarkers with a compulsive drinking behavior phenotype in rats. Rats that were selected for low drinking vs high drinking behavior following schedule-induced polydipsia (SIP) were assessed in a latent inhibition (LI) paradigm using tone and electrical foot shock and in a spatial reversal learning task to evaluate behavioral inflexibility. We also analyzed the myelin basic protein in different brain areas of high drinker (HD) and low drinker (LD) rats. The HD rats, which were characterized by a compulsive drinking behavior on SIP, had a reduced level of LI effect and increased behavioral inflexibility in the spatial reversal learning task in comparison to the LD group. Moreover, HD rats showed less myelination in the center of the corpus callosum, striatum, and amygdala in comparison to LD rats. These findings strengthen the validity of HD rats that were selected by SIP as a possible phenotype of compulsive neuropsychiatric disorders, as evidenced by the existence of behaviors and biological markers that are related to schizophrenia and obsessive-compulsive disorder, including a reduced LI effect, behavioral inflexibility and reduced brain myelination. Future studies could contribute to the elucidation of the mechanisms underlying the compulsive phenotype of HD rats and its relation to vulnerability to schizophrenia.

Compulsive sexual behavior: Prefrontal and limbic volume and interactions.

BACKGROUND: Compulsive sexual behaviors (CSB) are relatively common and associated with significant personal and social dysfunction. The underlying neurobiology is still poorly understood. The present study examines brain volumes and resting state functional connectivity in CSB compared with matched healthy volunteers (HV). METHODS: Structural MRI (MPRAGE) data were collected in 92 subjects (23 CSB males and 69 age-matched male HV) and analyzed using voxel-based morphometry. Resting state functional MRI data using multi-echo planar sequence and independent components analysis (ME-ICA) were collected in 68 subjects (23 CSB subjects and 45 age-matched HV). RESULTS: CSB subjects showed greater left amygdala gray matter volumes (small volume corrected, Bonferroni adjusted P < 0.01) and reduced resting state functional connectivity between the left amygdala seed and bilateral dorsolateral prefrontal cortex (whole brain, cluster corrected FWE P < 0.05) compared with HV. CONCLUSIONS: CSB is associated with elevated volumes in limbic regions relevant to motivational salience and emotion processing, and impaired functional connectivity between prefrontal control regulatory and limbic regions. Future studies should aim to assess longitudinal measures to investigate whether these findings are risk factors that predate the onset of the behaviors or are consequences of the behaviors. Hum Brain Mapp 38:1182-1190, 2017. © 2016 Wiley Periodicals, Inc.

Putamen volume correlates with obsessive compulsive characteristics in healthy population.

Obsessions and compulsions (OCs) are frequent in healthy subjects; however neural backgrounds of the subclinical OCs were largely unknown. Results from recent studies suggested involvement of the putamen in the OC traits. To investigate this issue, 49 healthy subjects were assessed using structural magnetic resonance imaging (MRI) and the Maudsley Obsessive Compulsive Inventory (MOCI). Anatomical delineation on MRI yielded the global volume and local shape of the putamen. Other striatal structures (the caudate nucleus and globus pallidus) were also examined for exploratory purpose. The relationship between volume/shape of each structures and MOCI measure was analyzed, with sex, age, state anxiety, trait anxiety, and full-scale Intelligence Quotient regressed out. The volume analysis revealed a positive relationship between the MOCI total score and the bilateral putamen volumes. The shape analysis demonstrated associations between the higher MOCI total score and hypertrophy of the anterior putamen in both hemispheres. The present study firstly revealed that the volume changes of the putamen correlated with the manifestation of subclinical OC traits. The dysfunctional cortico-anterior striatum networks seemed to be one of the neuronal subsystems underlying the subclinical OC traits.

Neonatal hypoxia-ischemia induces attention-deficit hyperactivity disorder-like behavior in rats.

Attention-deficit hyperactivity disorder (ADHD) may be caused by genetic or environmental factors. Among environmental factors, perinatal complications are related, such as neonatal hypoxia-ischemia (HI). Thus, the aim of this study was to investigate whether HI contributes to the development of characteristics related to ADHD in adult rats, and to correlate the behavioral results with brain damage volume. Male Wistar rats were divided into 2 groups: HI and control. The HI procedure consisted of a permanent occlusion of the right common carotid artery followed by a period of hypoxia (90 min; 8% O2 and 92% N2) on the 7th postnatal day. Two months later, animals were evaluated in the open field test during a single 5-min session, and in the 5-choice serial reaction time task (5-CSRTT), over 25 weeks. Our results demonstrated that animals submitted to HI manifest cognitive impairments in task acquisition, deficits in sustained attention, and increases in impulsivity and compulsivity in response to task manipulation in the 5-CSRTT. Locomotor activity observed in open field did not differ between groups. Moreover, brain volume loss in the total hemisphere, cerebral cortex, white matter, hippocampus, and striatum were observed in HI animals, especially on the side ipsilateral to the lesion. From these results, we can infer that neonatal HI is an environmental factor that could contribute to the development of behavioral characteristics observed in ADHD that are associated with general brain atrophy.

Schedule-induced polydipsia is associated with increased spine density in dorsolateral striatum neurons.

Schedule-induced polydipsia (SIP) is an adjunctive behavior in which rats exhibit excessive drinking as a consequence of intermittent feeding, and it has been proposed as a candidate model to study the development of compulsive and repetitive behavior. Although several brain structures are involved in compulsive behavior, it has been suggested that alterations in fronto-striatal circuits may underlie compulsive spectrum disorders. In the present work, we examined whether SIP would induce modifications in dorsolateral striatum (DLS) and anterior prefrontal cortex (aPFC) neurons. Specifically, the effects of 20 sessions of SIP were determined in the dendrites of DLS medium spiny neurons and in the basal dendritic arbors of layer V pyramidal cells in the aPFC. The structure, size and branching complexity in aPFC neurons were also studied. Results showed that SIP resulted in an increase in dendritic spine density in DLS neurons. Moreover, dendritic spine density was highly correlated with the level of drinking in animals subjected to SIP. By contrast, we observed no differences either in dendritic spine density or in the morphological structure of the dendrites of the aPFC in SIP rats compared to their control counterparts. We hypothesize that SIP-induced structural plasticity in DLS neurons could be related to inflexible response in compulsive behavior. The findings of this study could provide new insights into the involvement of particular cell populations of the dorsolateral striatum and anterior prefrontal cortex regions in compulsive spectrum disorders.

Abnormal gray matter and white matter volume in 'Internet gaming addicts'.

Internet gaming addiction (IGA) is usually defined as the inability of an individual to control his/her use of the Internet with serious negative consequences. It is becoming a prevalent mental health concern around the world. To understand whether Internet gaming addiction contributes to cerebral structural changes, the present study examined the brain gray matter density and white matter density changes in participants suffering IGA using voxel-based morphometric analysis. Compared with the healthy controls (N=36, 22.2 ± 3.13 years), IGA participants (N=35, 22.28 ± 2.54 years) showed significant lower gray matter density in the bilateral inferior frontal gyrus, left cingulate gyrus, insula, right precuneus, and right hippocampus (all p<0.05). IGA participants also showed significant lower white matter density in the inferior frontal gyrus, insula, amygdala, and anterior cingulate than healthy controls (all p<0.05). Previous studies suggest that these brain regions are involved in decision-making, behavioral inhibition and emotional regulation. Current findings might provide insight in understanding the biological underpinnings of IGA.

Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours.

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions.

New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity.

Impulsivity and compulsivity represent useful conceptualizations that involve dissociable cognitive functions, which are mediated by neuroanatomically and neurochemically distinct components of cortico-subcortical circuitry. The constructs were historically viewed as diametrically opposed, with impulsivity being associated with risk-seeking and compulsivity with harm-avoidance. However, they are increasingly recognized to be linked by shared neuropsychological mechanisms involving dysfunctional inhibition of thoughts and behaviors. In this article, we selectively review new developments in the investigation of the neurocognition of impulsivity and compulsivity in humans, in order to advance our understanding of the pathophysiology of impulsive, compulsive, and addictive disorders and indicate new directions for research.