Dimensionality of Cognitions in Behavioral Addiction.

Cognitive constructs provide conceptual frameworks for transpathological characterization and improved phenotyping of apparently disparate psychiatric groups. This dimensional approach can be applied to the examination of individuals with behavioral addictions, for example, towards gambling, video-games, the internet, food, and sex, allowing operationalization of core deficits. We use this approach to review constructs such as impulsivity, compulsivity, and attention regulation, which may be most relevant, applicable, and successful for the understanding and subsequent treatment of the addictions.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s40473-016-0068-

Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels

Objective Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [11C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [123I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. Methods The [123I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. Results Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. Conclusions Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications

Reward Sensitivity and Waiting Impulsivity: Shift towards Reward Valuation away from Action Control

Background: Impulsivity and reward expectancy are commonly inter-related. Waiting impulsivity, measured using the rodent 5-Choice Serial Reaction Time (5-CSRT) task, predicts compulsive cocaine seeking and sign (or cue) tracking. Here we assess human waiting impulsivity using a novel translational task, the 4-CSRT, and the relationship with reward cues. Methods: Healthy volunteers (n=29) performed the monetary incentive delay task as a functional MRI study where subjects observe a cue predicting reward (cue) and wait to respond for high (£5), low (£1) or no reward. Waiting impulsivity was tested with the 4-CSRT. Results: For high reward prospects (£5 – no reward), greater waiting impulsivity on the 4-CSRT correlated with greater medial orbitofrontal cortex (OFC) and lower supplementary motor area (SMA) activity to cues. In response to high reward cues, greater waiting impulsivity was associated with greater subthalamic nucleus connectivity with OFC and greater subgenual cingulate connectivity with anterior insula but decreased connectivity with regions implicated in action selection and preparation. Conclusion: These findings highlight a shift towards regions implicated in reward valuation and a shift towards compulsivity away from higher level motor preparation and action selection and response. We highlight the role of reward sensitivity and impulsivity, mechanisms potentially linking human waiting impulsivity with incentive approach and compulsivity, theories highly relevant to disorders of addiction.This work was supported by the Wellcome Trust Fellowship grant for V.V. (093705/Z/10/Z). V.V. is currently supported by a Medical Research Council Senior Fellowship (MR/P008747/1). N.D. is a research fellow of the Deutsche Forschungsgemeinschaft (DO1915/1-1). The BCNI is supported by a WT and MRC grant

Disrupted resting-state brain network properties in obesity: decreased global and putaminal cortico-striatal network efficiency.

BACKGROUND: The efficient organization and communication of brain networks underlie cognitive processing and their disruption can lead to pathological behaviours. Few studies have focused on whole-brain networks in obesity and binge eating disorder (BED). Here we used multi-echo resting-state functional magnetic resonance imaging (rsfMRI) along with a data-driven graph theory approach to assess brain network characteristics in obesity and BED. METHOD: Multi-echo rsfMRI scans were collected from 40 obese subjects (including 20 BED patients) and 40 healthy controls and denoised using multi-echo independent component analysis (ME-ICA). We constructed a whole-brain functional connectivity matrix with normalized correlation coefficients between regional mean blood oxygenation level-dependent (BOLD) signals from 90 brain regions in the Automated Anatomical Labeling atlas. We computed global and regional network properties in the binarized connectivity matrices with an edge density of 5%-25%. We also verified our findings using a separate parcellation, the Harvard-Oxford atlas parcellated into 470 regions. RESULTS: Obese subjects exhibited significantly reduced global and local network efficiency as well as decreased modularity compared with healthy controls, showing disruption in small-world and modular network structures. In regional metrics, the putamen, pallidum and thalamus exhibited significantly decreased nodal degree and efficiency in obese subjects. Obese subjects also showed decreased connectivity of cortico-striatal/cortico-thalamic networks associated with putaminal and cortical motor regions. These findings were significant with ME-ICA with limited group differences observed with conventional denoising or single-echo analysis. CONCLUSIONS: Using this data-driven analysis of multi-echo rsfMRI data, we found disruption in global network properties and motor cortico-striatal networks in obesity consistent with habit formation theories. Our findings highlight the role of network properties in pathological food misuse as possible biomarkers and therapeutic targets.The study was funded by the Wellcome Trust Fellowship grant for V.V. (093705/Z/10/Z) and the Cambridge National Institute for Health Research (NIHR) Biomedical Research Centre. We thank Dr Ameera Patel for providing the H-O470 brain parcellation atlas in the present study.This is the final version of the article. It first appeared from Cambridge University Press via https://doi.org/10.1017/S003329171600264

Shallow Basin Structure and Attenuation Are Key to Predicting Long Shaking Duration in Los Angeles Basin

Ground motions in the Los Angeles Basin during large earthquakes are modulated by earthquake ruptures, path effects into the basin, basin effects, and local site response. We analyzed the direct effect of shallow basin structures on shaking duration at a period of 2–10 s in the Los Angeles region through modeling small magnitude, shallow, and deep earthquake pairs. The source depth modulates the basin response, particularly the shaking duration, and these features are a function of path effect and not site condition. Three‐dimensional simulations using the CVM‐S4.26.M01 velocity model show good fitting to the initial portion of the waveforms at periods of 5 s and longer but fail to predict the long shaking duration during shallow events, especially at periods less than 5 s. Simulations using CVM‐H do not match the timing of the initial arrivals as well as CVM‐S4.26.M01, and the strong late arrivals in the CVM‐H simulation travel with an apparent velocity slower than observed. A higher‐quality factor than traditionally assumed may produce synthetics with longer durations but is unable to accurately match the amplitude and phase. Beamforming analysis using dense array data further reveals the long duration surface waves have the same back azimuth as the direct arrivals and are generated at the basin edges, while the later coda waves are scattered from off‐azimuth directions, potentially due to strong, sharp boundaries offshore. Improving the description of these shallow basin structures and attenuation model will enhance our capability to predict long‐period ground motions in basins

Distinct cortico-striatal connections with subthalamic nucleus underlie facets of compulsivity

The capacity to flexibly respond to contextual changes is crucial to adapting to a dynamic environment. Compulsivity, or behavioural inflexibility, consists of heterogeneous subtypes with overlapping yet discrete neural substrates. The subthalamic nucleus (STN) mediates the switch from automatic to controlled processing to slow, break or stop behaviour when necessary. Rodent STN lesions or inactivation are linked with perseveration or repetitive, compulsive responding. However, there are few studies examining the role of latent STN-centric neural networks and compulsive behaviour in healthy individuals. We therefore aimed to characterize the relationship between measures of compulsivity (goal-directed and habit learning, perseveration, and self-reported obsessive - compulsive symptoms) and the intrinsic resting state network of the STN. We scanned 77 healthy controls using a multi-echo resting state functional MRI sequence analyzed using independent components analysis (ME-ICA) with enhanced signal-to-noise ratio to examine small subcortical structures. Goal directed model-based behaviour was associated with higher connectivity of STN with medial orbitofrontal cortex (mOFC) and ventral striatum (VS) and more habitual model-free learning was associated with STN connectivity with hippocampus and dorsal anterior cingulate cortex (ACC). Perseveration was associated with reduced connectivity between STN and premotor cortex and finally, higher obsessive -compulsive inventory scores were associated with reduced STN connectivity with dorsolateral prefrontal cortex (PF). We highlight unique contributions of diffuse cortico-striatal functional connections with STN in dissociable measures of compulsivity. These findings are relevant to the development of potential biomarkers of treatment response in neurosurgical procedures targeting the STN for neurological and psychiatric disorders.This study was funded by the Wellcome Trust Fellowship grant for VV (093705/Z/10/Z)

Shallow Basin Structure and Attenuation Are Key to Predicting Long Shaking Duration in Los Angeles Basin

Ground motions in the Los Angeles Basin during large earthquakes are modulated by earthquake ruptures, path effects into the basin, basin effects, and local site response. We analyzed the direct effect of shallow basin structures on shaking duration at a period of 2–10 s in the Los Angeles region through modeling small magnitude, shallow, and deep earthquake pairs. The source depth modulates the basin response, particularly the shaking duration, and these features are a function of path effect and not site condition. Three‐dimensional simulations using the CVM‐S4.26.M01 velocity model show good fitting to the initial portion of the waveforms at periods of 5 s and longer but fail to predict the long shaking duration during shallow events, especially at periods less than 5 s. Simulations using CVM‐H do not match the timing of the initial arrivals as well as CVM‐S4.26.M01, and the strong late arrivals in the CVM‐H simulation travel with an apparent velocity slower than observed. A higher‐quality factor than traditionally assumed may produce synthetics with longer durations but is unable to accurately match the amplitude and phase. Beamforming analysis using dense array data further reveals the long duration surface waves have the same back azimuth as the direct arrivals and are generated at the basin edges, while the later coda waves are scattered from off‐azimuth directions, potentially due to strong, sharp boundaries offshore. Improving the description of these shallow basin structures and attenuation model will enhance our capability to predict long‐period ground motions in basins

Interferon-alpha induced changes in NODDI predispose to the development of fatigue

Interferon-alpha (IFN-α) is an important mediator of antiviral immune responses. It is also used clinically in the treatment of hepatitis-C infection. Though effective, IFN-α-based therapies can often impair mood, motivation and cognition, which when severe can appear indistinguishable from major depression. In susceptible patients, fatigue and motivational impairment emerge early and have been linked to changes in basal ganglia (striatal) metabolism, neurochemistry and microstructural integrity. Here we use neurite orientation dispersion and density imaging (NODDI) modeling of multi-shell diffusion MRI to investigate whether changes in orientation dispersion index (ODI) or neurite density index (NDI) can predict the later emergence of IFN-α-induced fatigue. Eighteen patients initiating IFN-α based treatment for hepatitis-C underwent diffusion MRI and blood sampling at baseline and 4 hours after their first IFN-α injection. They were then followed up with regular psychological assessments for 12 weeks of treatment. IFN-α injection stimulated an acute inflammatory cytokine response and evoked acute fatigue that peaked between 4 and 12 weeks of treatment. Within the brain, IFN-α induced an acute increase in NDI in patients that experienced a simultaneous increase in IFN-α-induced fatigue but not patients that did not. Acute changes in striatal microstructure additionally predicted the continued development of fatigue but not mood symptoms 4 and 8 weeks later into treatment. Our findings highlight the value of NODDI as a potential in vivo biomarker of the central effects of peripheral inflammation. We highlight the exquisite sensitivity of the striatum to IFN-α and further implicate striatal perturbation in IFN-α-induced fatigue

Impulsivity in disorders of food and drug misuse.

BACKGROUND: Evidence suggests some overlap between the pathological use of food and drugs, yet how impulsivity compares across these different clinical disorders remains unclear. Substance use disorders are commonly characterized by elevated impulsivity, and impulsivity subtypes may show commonalities and differences in various conditions. We hypothesized that obese subjects with binge-eating disorder (BED) and abstinent alcohol-dependent cohorts would have relatively more impulsive profiles compared to obese subjects without BED. We also predicted decision impulsivity impairment in obesity with and without BED. METHOD: Thirty obese subjects with BED, 30 without BED and 30 abstinent alcohol-dependent subjects and age- and gender-matched controls were tested on delay discounting (preference for a smaller immediate reward over a larger delayed reward), reflection impulsivity (rapid decision making prior to evidence accumulation) and motor response inhibition (action cancellation of a prepotent response). RESULTS: All three groups had greater delay discounting relative to healthy volunteers. Both obese subjects without BED and alcohol-dependent subjects had impaired motor response inhibition. Only obese subjects without BED had impaired integration of available information to optimize outcomes over later trials with a cost condition. CONCLUSIONS: Delay discounting appears to be a common core impairment across disorders of food and drug intake. Unexpectedly, obese subjects without BED showed greater impulsivity than obese subjects with BED. We highlight the dissociability and heterogeneity of impulsivity subtypes and add to the understanding of neurocognitive profiles across disorders involving food and drugs. Our results have therapeutic implications suggesting that disorder-specific patterns of impulsivity could be targeted.V.V. is a Wellcome Trust Intermediate Fellow in Clinical Neurosciences (Wellcome Trust grant no. WT093705MA). Y.W. is supported by the Fyssen Fondation. N.A.H. is a Wellcome Trust Intermediate Fellow in Clinical Neurosciences. The BCNI is supported by both the Wellcome Trust and Medical Research Council.This is the accepted manuscript. The final version is available from CUP at http://dx.doi.org/10.1017/S003329171400183

The relative balance of goal-directed and habitual behaviours in obsessive-compulsive disorder

Our decisions are based on parallel and competing systems of goal-directed and habitual learning, systems which can be impaired in pathological behaviours. Here we focus on the influence of motivation and compare reward and loss outcomes in subjects with obsessive-compulsive disorder (OCD) on model-based goal-directed and model-free habitual behaviours using the two-step task. We further investigate the relationship with acquisition learning using a one-step probabilistic learning task. Forty-eight OCD subjects and 96 healthy volunteers were tested on a reward and 30 OCD subjects and 53 healthy volunteers on the loss version of the two-step task. Thirty-six OCD subjects and 72 healthy volunteers were also tested on a one-step reversal task. OCD subjects compared with healthy volunteers were less goal oriented (model-based) and more habitual (model-free) to reward outcomes with a shift towards greater model-based and lower habitual choices to loss outcomes. OCD subjects also had enhanced acquisition learning to loss outcomes on the one-step task, which correlated with goal-directed learning in the two-step task. OCD subjects had greater stay behaviours or perseveration in the one-step task irrespective of outcome. Compulsion severity was correlated with habitual learning in the reward condition. Obsession severity was correlated with greater switching after loss outcomes. In healthy volunteers, we further show that greater reward magnitudes are associated with a shift towards greater goal-directed learning further emphasizing the role of outcome salience. Our results highlight an important influence of motivation on learning processes in OCD and suggest that distinct clinical strategies based on valence may be warranted.The study was funded through a Wellcome Trust Intermediate Clinical Fellowship for VV (093705/Z/10/Z).This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/tp.2015.16