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

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

Observations on the effects of feeding moldy corn to rats

Twenty rats (10 males, 10 females) averaging 35 g were randomly allotted, in groups of 5, to 2 treatments using fresh corn and corn purchased from a feed dealer and suspected to have high mycotoxins. The various organs were compared to determine the effects of the treatment on the development of the specific organs. The analysis of variance showed significant difference (P < 0.001) in average daily gain, average daily feed and feed conversion ratio for the 2 different treatments. There was also a slight treatment .times. sex interaction. Rats fed fresh corn performed better than rats fed purchased corn. Male rats fed fresh corn performed better than female rats whereas the reverse was true for rats fed moldy corn. There was no treatment effect on liver size but liver weight was significantly (P < 0.05) different between sexes. Uterus weight of rats on different treatments were significantly different (P < 0.001) and depressed development of sex organs. Rats given moldy corn had larger kidneys (P < 0.005) than rats fed fresh corn

Real exchange rate dynamics in the Asian economies: can regime shifts explain purchasing power parity puzzles?

We show that the strong version of the purchasing power parity (PPP) hypothesis holds in most of the US dollar real exchange rates using cointegration method that accounts for breaks in the models. The break dates in seven of the Asian currencies coincide with the two rounds of currency depreciation recorded during the 1997–1998 financial crises. We obtain a mean half-life estimate of about 10 months for PPP to converge to its long-run equilibrium level. Our confidence intervals based on persistence profile approach for the half-lives is much narrower than previous evidence might indicate. Taken together, these results show that mean reversion is stronger than commonly thought

Drug utilization study of antihypertensive drugs in a clinic in Malaysia

Background: Hypertension is one of the common chronic diseases resulting in high mortality and morbidity. A plethora of new drugs are now available, and the quality of life for these patients has been altered for the better. Not many studies are conducted in Malaysia regarding drug utilization of antihypertensives and hence this study was planned.Methods: This was a pilot study conducted in a private clinic in Kuala Lumpur. Thirty patients with hypertension were chosen randomly and their prescriptions were analyzed. The data was collected in a proforma designed for the study. The proforma included variables such as age, gender, drugs used, and also regarding the names of the drugs used (generic or trade). The data was analyzed using descriptive statistics.Results: Thirty patients were recruited for the study. We found that 53% of the patients were females and 47% males. Trade names were more commonly used i.e. 64% of patients, than the generic names. Monotherapy (70%) was more frequently used than combination drugs. Beta blockers (45%) were used more often followed by calcium channel blockers (25%).Conclusions: The incidence of polypharmacy was low. The three most common groups of drugs used in hypertension were beta blockers followed by calcium channel blockers and then angiotensin converting enzyme inhibitors. Drug utilization studies are powerful exploratory tools to ascertain the role of drugs in society.

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)

Port assisted closure of laparoscopic wound: A safe and feasible technique

Objective: Various techniques and instruments have been developed to provide safe and secure closure of laparoscopic wounds. Herein we describe a simple method to close laparoscopic supraumbilical wounds with the aid of a laparoscopic port. Method: This was a retrospective review of prospective data, which were from 151 patients who underwent laparoscopic cholecystectomy for symptomatic gallstone disease from December 2009 to December 2010 in Sultanah Bahiyah Hospital. A senior consultant hepato-pancreato-biliary (HPB) surgeon and two HPB trainee surgeons performed the operations. Postoperatively, all patients were followed up at 4 weeks. Results: All patients successfully underwent closure of the supraumbilical wound with the assistance of a 5mm laparoscopic port. None of the patients had incisional hernia on follow up. Conclusion: Port assisted closure of supraumbilical laparoscopic wounds is a feasible and safe technique

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

The involuntary nature of binge drinking: goal directedness and awareness of intention

Binge drinking represents a public health issue and is a known risk factor in the development of alcohol use disorders. Previous studies have shown behavioural as well as neuroanatomical alterations associated with binge drinking. Here, we address the question of the automaticity or involuntary nature of the behaviour by assessing goal-directed behaviour and intentionality. In this study, we used a computational two-step task, designed to discern between model-based/goal-directed and model-free/habitual behaviours, and the classic Libet clock task, to study intention awareness, in a sample of 31 severe binge drinkers (BD) and 35 matched healthy volunteers. We observed that BD had impaired goal-directed behaviour in the two-step task compared with healthy volunteers. In the Libet clock task, BD showed delayed intention awareness. Further, we demonstrated that alcohol use severity, as reflected by the alcohol use disorders identification test, correlated with decreased conscious awareness of volitional intention in BD, although it was unrelated to performance on the two-step task. However, the time elapsed since the last drinking binge influenced the model-free scores, with BD showing less habitual behaviour after longer abstinence. Our findings suggest that the implementation of goal-directed strategies and the awareness of volitional intention are affected in current heavy alcohol users. However, the modulation of these impairments by alcohol use severity and abstinence suggests a state effect of alcohol use in these measures and that top-down volitional control might be ameliorated with alcohol use cessation.N.D. is a research fellow of the Deutsche Forschungsgemeinschaft (DO1915/1-1). This study was funded by the Wellcome Trust as part of a Wellcome Trust Intermediate Fellowship to V.V. (983705/Z/10/Z). V.V. is funded by a Medical Research Council Senior Fellowship (MR/P008747/1)