Serum Irisin, Adropin, and Preptin in Obese Patients 6 Months After Bariatric Surgery.

BACKGROUND/OBJECTIVES: The reduction of body mass after bariatric surgery affects energy metabolism and may involve changes in irisin, preptin, and adropin production. SUBJECTS AND METHODS: Fifty-five morbidly obese patients with a mean body mass index (BMI) of 45.7 ± 5.8 kg/m2 were treated with either laparoscopic sleeve gastrectomy(n = 30) or laparoscopic adjustable gastric banding (n = 25). Forty-six (83.6%) were followed-up 6 months after surgery. The control group included 15 healthy non-obese participants. Anthropometric measurements, lipid profiles, HbA1c, and serum irisin, preptin, and adropin were assessed at baseline and on follow-up. RESULTS: The serum concentrations of all three peptides were higher at 6 months than at baseline but only irisin (p = 0.02) and adropin (p = 0.000001) were significantly higher. The increase in preptin was borderline significant (p = 0.051). Changes of serum concentrations of all three peptides were bidirectional. CONCLUSION: Body mass reduction resulting from bariatric procedures may change the production of energy regulating peptides, but not always in a favorable manner.

Impact of sleeve gastrectomy on red blood cell aggregation: a 12-month follow-up study.

OBJECTIVE: To investigate the effects of weight loss due to laparoscopic sleeve gastrectomy (LSG) on erythrocyte aggregation and the relationship of anthropometric and plasmatic factors, such as plasma viscosity, fibrinogen and lipids, with erythrocyte aggregation. DESIGN AND SUBJECTS: The RBC aggregation and kinetics of the red blood cell aggregation were performed by the Laser-assisted Optical Rotational Cell Analyser (LORCA). Before the LSG and 6 and 12 months after the LSG, we evaluated the aggregation index (AI), amplitude (AMP) and aggregation half-time (t1/2), plasma viscosity, fibrinogen, glucose and lipids patterns in 15 non-diabetic obese subjects. RESULTS: The static and kinetic parameters of aggregation in obese patients at each time point after bariatric weight loss surgery were calculated and significant differences were observed at 12 months after surgery. AI and AMP decreased from 69.81±5.12% and 27.43±2.9 a.u. at baseline to 64.91±5.94% and 22.15±4.3 a.u. 12 months after surgery, respectively. The t1/2 increased from 1.7 (1.32-2.24) s at baseline compared with 2.02 (1.68-2.42) s at 12 months after the surgery. Plasma viscosity and fibrinogen decreased from 1.50±0.093 mPa s and 3.0±0.41 g l(-1) at baseline to 1.407±0.062 mPa s and to 2.66±0.25 g l(-1) 12 months after surgery, respectively. AI correlated positively with BMI (r=0.74, P=0.001), waist circumference (r=0.68, P=0.005), fibrinogen (r=0.52, P=0.045) and plasma viscosity (r=0.76, P=0.001) and negatively with percentages of weight lost after surgery (r=-0.54, P=0.034). Multivariate analyses found that the BMI, fibrinogen and plasma viscosity independently influenced the AI. CONCLUSION: The study demonstrated that weight loss due to restrictive bariatric surgery can beneficially affect red cell aggregation parameters. The improvement of the RBC aggregation behaviours among obese subjects with weight loss due to LSG was associated with changes in plasmatic factors, especially fibrinogen.

Cortisol and ghrelin concentrations following a cold pressor stress test in overweight individuals with and without night eating.

OBJECTIVE: To explore appetite-related hormones following stress in overweight individuals, and their relationship with night eating (NE) status. METHOD: We measured plasma cortisol and ghrelin concentrations, and recorded ratings of stress and hunger in response to a physiological laboratory stressor (cold pressor test, CPT), in overweight women with (n=11; NE) and without (n=17; non-NE) NE. RESULTS: Following the CPT, cortisol (P<0.001) and ghrelin (P<0.05) levels increased, as did stress and hunger ratings (all P<0.001), across all subjects (NE and non-NE). NE exhibited higher baseline cortisol (P<0.05) levels than non-NE. NE also had greater cortisol area under the curve (AUC) than non-NE (P=0.019), but not when controlling for baseline cortisol levels. Ghrelin baseline and AUC did not differ between groups. NE showed higher AUC stress (P<0.05), even when controlling for baseline stress. DISCUSSION: Overweight individuals showed increased cortisol, ghrelin, stress and hunger following a laboratory stressor, and there was some evidence for greater increases in cortisol and subjective stress among NE. The greater AUC cortisol level in NE was due to higher baseline levels, but the group difference in stress was in direct response to the stressor. Our results support a role for cortisol and stress in NE.

Novel age-dependent learning deficits in a mouse model of Alzheimer's disease: implications for translational research.

Computational modeling predicts that the hippocampus plays an important role in the ability to apply previously learned information to novel problems and situations (referred to as the ability to generalize information or simply as 'transfer learning'). These predictions have been tested in humans using a computer-based task on which individuals with hippocampal damage are able to learn a series of complex discriminations with two stimulus features (shape and color), but are impaired in their ability to transfer this information to newly configured problems in which one of the features is altered. This deficit occurs despite the fact that the feature predictive of the reward (the relevant information) is not changed. The goal of the current study was to develop a mouse analog of transfer learning and to determine if this new task was sensitive to pathological changes in a mouse model of AD. We describe a task in which mice were able to learn a series of concurrent discriminations that contained two stimulus features (odor and digging media) and could transfer this learned information to new problems in which the irrelevant feature in each discrimination pair was altered. Moreover, we report age-dependent deficits specific to transfer learning in APP+PS1 mice relative to non-transgenic littermates. The robust impairment in transfer learning may be more sensitive to AD-like pathology than traditional cognitive assessments in that no deficits were observed in the APP+PS1 mice on the widely used Morris water maze task. These data describe a novel and sensitive paradigm to evaluate mnemonic decline in AD mouse models that has unique translational advantages over standard species-specific cognitive assessments (e.g., water maze for rodent and delayed paragraph recall for humans).

A neurocomputational model of tonic and phasic dopamine in action selection: a comparison with cognitive deficits in Parkinson's disease.

The striatal dopamine signal has multiple facets; tonic level, phasic rise and fall, and variation of the phasic rise/fall depending on the expectation of reward/punishment. We have developed a network model of the striatal direct pathway using an ionic current level model of the medium spiny neuron that incorporates currents sensitive to changes in the tonic level of dopamine. The model neurons in the network learn action selection based on a novel set of mathematical rules that incorporate the phasic change in the dopamine signal. This network model is capable of learning to perform a sequence learning task that in humans is thought to be dependent on the basal ganglia. When both tonic and phasic levels of dopamine are decreased, as would be expected in unmedicated Parkinson's disease (PD), the model reproduces the deficits seen in a human PD group off medication. When the tonic level is increased to normal, but with reduced phasic increases and decreases in response to reward and punishment, respectively, as would be expected in PD medicated with L-Dopa, the model again reproduces the human data. These findings support the view that the cognitive dysfunctions seen in Parkinson's disease are not solely either due to the decreased tonic level of dopamine or to the decreased responsiveness of the phasic dopamine signal to reward and punishment, but to a combination of the two factors that varies dependent on disease stage and medication status.

Comparison of eating disorders and body image disturbances between Eastern and Western countries.

Factors associated with the development of eating disorders in countries with non-Western cultures have not been adequately investigated in relation to Westernized countries. We therefore studied 243 girls [age =16.5+/-1.2 (SD)], recruited from schools in India, Tibet, the US and France. They completed the Figure Rating Scale (FRS), the Eating Attitudes Test (EAT), and the Beck Depression Inventory (BDI). The Tibetan group had a lower body mass index (BMI) than the other groups (p<0.0001), which did not differ from each other. All groups differed significantly on socio-economic status (SES), with those living in India having the highest (p<0.0001). Prior to controlling for age, SES, and BMI, there were no significant differences on any psychological measure between the individual countries, or when collapsed by East vs. West. However, after controlling for the same covariates, the Tibetan group selected a significantly larger current (p<0.0001) and ideal body size (p=0.03), compared to all the other countries, and had more body image discrepancy than the American group (p=0.04). After controlling only for BMI, the girls from the East had a larger current and ideal, but no difference on body image discrepancy. Body image discrepancy scores were best predicted by EAT scores and BMI, accounting for 35% of the variance (p<0.0001). EAT scores themselves were best predicted by mother's education, BDI, body image discrepancy, and drug and tobacco use, accounting for 33% of the variance (p<0.0001). Unlike some other studies, we did not observe greater body image discrepancy and eating pathology in Western cultures, whether or not controlling for age, SES, and BMI. There were no differences in eating and depression pathology between those in the US, France, or India. Indeed, the Tibetans, after controlling for their low BMI and SES, had the greatest body image discrepancy.

Probabilistic categorization: how do normal participants and amnesic patients do it?

In probabilistic categorization tasks, various cues are probabilistically (but not perfectly) predictive of class membership. This means that a given combination of cues sometimes belongs to one class and sometimes to another. It is not yet clear how categorizers approach such tasks. Here, we review evidence in favor of two alternative conceptualizations of learning in probabilistic categorization: as rule-based learning, or as incremental learning. Each conceptualization forms the basis of a way of analyzing performance: strategy analysis assumes rule-based learning, while rolling regression analysis assumes incremental learning. Here, we contrasted the ability of each to predict performance of normal categorizers. Both turned out to predict responses about equally well. We then reviewed performance of patients with damage to regions deemed important for either rule-based or incremental learning. Evidence was again about equally compatible with either alternative conceptualization of learning, although neither predicted an involvement of the medial temporal lobe. We suggest that a new way of conceptualizing probabilistic categorization might be fruitful, in which the medial temporal lobe help set up representations that are then used by other regions to assign patterns to categories.

Night eating status and influence on body weight, body image, hunger, and cortisol pre- and post- Roux-en-Y Gastric Bypass (RYGB) surgery.

Night Eating Syndrome is a common disorder in severely obese individuals and may be associated with hypothalamic pituitary adrenal (HPA) axis dysregulation. This study compared night eaters (NE) and comparably obese controls (C) pre- and post-Roux-en- Y Gastric Bypass surgery at 2 and 5 months, following an overnight fast on hormonal measures associated with HPA axis and related appetite and psychological measures. There were 24 (10 NE, 14 C) clinically severely obese participants (body mass index =47.0+/-8.4 SD). At pre-surgery baseline, afternoon fasting hunger ratings differed significantly and were lower for NE than for C (p=0.01). Eight of the participants (4 NE, 4C) returned for all 3 study visits. At 5 months post-surgery, NE and C did not differ in weight loss, reductions in waist circumference, insulin levels, and insulin resistance (homeostasis model assessment). However, NE as compared to C, did not improve in self ratings of body image (p<0.05), and had significant increases in fasting afternoon cortisol levels 5 months after surgery (p=0.01).

Risk and protective haplotypes of the alpha-synuclein gene associated with Parkinson's disease differentially affect cognitive sequence learning.

Alpha-synuclein (SNCA) is a key factor in the regulation of dopaminergic transmission and is related to Parkinson's disease. In this study, we investigated the effects of risk and protective SNCA haplotypes associated with Parkinson's disease on cognitive sequence learning in 204 healthy volunteers. We found that the 3'-block risk SNCA haplotypes are associated with less effective stimulus-reward learning of sequences and with superior context representation of sequences. In contrast, participants with protective haplotypes exhibit better stimulus-reward learning and worse context representation, which suggest that these functions are inversely affected by risk and protective haplotypes. The Rep1 promoter polymorphism does not influence cognitive sequence learning. Because stimulus-reward learning may be mediated by the basal ganglia and context learning may be related to the medial temporal lobe, our data raise the possibility that dopaminergic signals regulated by SNCA inversely affect these memory systems.

Basal ganglia and dopamine contributions to probabilistic category learning.

Studies of the medial temporal lobe and basal ganglia memory systems have recently been extended towards understanding the neural systems contributing to category learning. The basal ganglia, in particular, have been linked to probabilistic category learning in humans. A separate parallel literature in systems neuroscience has emerged, indicating a role for the basal ganglia and related dopamine inputs in reward prediction and feedback processing. Here, we review behavioral, neuropsychological, functional neuroimaging, and computational studies of basal ganglia and dopamine contributions to learning in humans. Collectively, these studies implicate the basal ganglia in incremental, feedback-based learning that involves integrating information across multiple experiences. The medial temporal lobes, by contrast, contribute to rapid encoding of relations between stimuli and support flexible generalization of learning to novel contexts and stimuli. By breaking down our understanding of the cognitive and neural mechanisms contributing to different aspects of learning, recent studies are providing insight into how, and when, these different processes support learning, how they may interact with each other, and the consequence of different forms of learning for the representation of knowledge.

Dopaminergic contribution to cognitive sequence learning.

Evidence suggests that dopaminergic mechanisms in the basal ganglia are important in feedback-guided habit learning. To test hypothesis, we assessed cognitive sequence learning in 120 healthy volunteers and measured plasma levels of homovanillic acid [HVA] (a metabolite of dopamine), 5-hydroxyindoleacetic acid [5-HIAA] (a metabolite of serotonin), and 3-methoxy-4-hydroxypheylglycol [MHPG] (a metabolite of norepinephrine). Results revealed a significant negative relationship between errors in the feedback-guided training phase of the sequence learning task and the plasma HVA level. The HVA level accounted for 10.5% of variance of performance. Participant who had lower HVA level than the median value of the whole sample committed more errors during the training phase compared with participants who had higher HVA plasma level than the median value. A similar phenomenon was not observed for the context-dependent phase of the task and for 5-HIAA and MHPG. These results suggest that dopamine plays a special role in feedback-guided cognitive sequence learning.

Conditional discrimination and reversal in amnesia subsequent to hypoxic brain injury or anterior communicating artery aneurysm rupture.

Human anterograde amnesia can develop following bilateral damage to the hippocampus and medial temporal lobes, as in hypoxic brain injury, or following damage to the basal forebrain, as following anterior communicating artery (ACoA) aneurysm rupture. In both cases, the mnestic deficit may be similar when assessed by standard neuropsychological measures. However, animal and computational models suggest that there are qualitative differences in the pattern of impaired and spared memory abilities following damage to hippocampus versus basal forebrain. Here, we show such a dissociation in human amnesia using a single two-stage task, involving conditional discrimination and reversal. Consistent with a prior study, 10 individuals with anterograde amnesia subsequent to hypoxic brain injury were spared on acquisition but impaired at reversal. However, 10 individuals with amnesia subsequent to ACoA aneurysm showed the opposite pattern of impaired acquisition but spared reversal. The differences between groups cannot be easily ascribed to severity of mnestic or cognitive deficit, since the two amnesic groups performed similarly on neuropsychological tests of memory, intelligence and attention. The results illustrate qualitative differences in memory impairments in hypoxic and ACoA amnesics and highlight the importance of considering etiology in evaluating mnemonic deficits in amnesic populations.

Biliopancreatic diversion in Poland.

Biliopancreatic diversion (BPD) is a bariatric operation of proved efficacy especially in patients with metabolic comorbidities. The aim was to assess the results of BPD in relation to weight loss and coexisting lipid and glucose metabolism disturbances in the Polish population. Between October 2001 and December 2003 57 morbidly obese patients (24 male and 33 female) underwent BPD. Median age was 46 years (range: 17-58) and median body mass index (BMI) was 50.2 kg/m(2) (range: 40.1-73 kg/m(2)). Type 2 diabetes mellitus was observed in 11 patients (19.3%), hypercholesterolaemia in 38 patients (66.7%) and hypertriglyceridaemia in 37 patients (64.9%). Median value of BMI decreased at three months to 40.0 kg/m(2), at six months to 36.7 kg/m(2), and after a year to 32.3 kg/m2. Diabetes was completely resolved in all patients. After six months, triglycerides and cholesterol levels were higher than normal only in one patient. Early specific complications that manifested as seroma and nosocomial pneumonia occurred in 5.3% and 3.5% patients, respectively. The following specific late complications were observed: ulceration of stomach stump (3.4%), anaemia (14.0%), hypoalbuminaemia (8.8%), deterioration of haemorrhoids (15.8). All of above complications were treated conservatively expect two haemorrhoidectomies. One patient died due to myocardial infarction eight months after BPD. Five cases of incisional hernias (8.8%) were found. BPD is an effective bariatric procedure also in the Polish population, resulting not only in weight loss but also in the improvement of lipid and glucose metabolism.

Radiatively generated isospin violations in the nucleon and the NuTeV anomaly.

Predictions of isospin asymmetries of valence and sea distributions are presented which are generated by QED leading Oalpha photon bremsstrahlung effects. Together with isospin violations arising from nonperturbative hadronic sources (such as quark and target mass differences) as well as with even a conservative contribution from a strangeness asymmetry (s not equal to s), the discrepancy between the large NuTeV anomaly result for sin(2Theta(w)) and the world average of other measurements is removed.

Integrating incremental learning and episodic memory models of the hippocampal region.

By integrating previous computational models of corticohippocampal function, the authors develop and test a unified theory of the neural substrates of familiarity, recollection, and classical conditioning. This approach integrates models from 2 traditions of hippocampal modeling, those of episodic memory and incremental learning, by drawing on an earlier mathematical model of conditioning, SOP (A. Wagner, 1981). The model describes how a familiarity signal may arise from parahippocampal cortices, giving a novel explanation for the finding that the neural response to a stimulus in these regions decreases with increasing stimulus familiarity. Recollection is ascribed to the hippocampus proper. It is shown how the properties of episodic representations in the neocortex, parahippocampal gyrus, and hippocampus proper may explain phenomena in classical conditioning. The model reproduces the effects of hippocampal, septal, and broad hippocampal region lesions on contextual modulation of classical conditioning, blocking, learned irrelevance, and latent inhibition.

Mitochondrial inhibition and oxidative stress: reciprocating players in neurodegeneration.

Although the etiology for many neurodegenerative diseases is unknown, the common findings of mitochondrial defects and oxidative damage posit these events as contributing factors. The temporal conundrum of whether mitochondrial defects lead to enhanced reactive oxygen species generation, or conversely, if oxidative stress is the underlying cause of the mitochondrial defects remains enigmatic. This review focuses on evidence to show that either event can lead to the evolution of the other with subsequent neuronal cell loss. Glutathione is a major antioxidant system used by cells and mitochondria for protection and is altered in a number of neurodegenerative and neuropathological conditions. This review also addresses the multiple roles for glutathione during mitochondrial inhibition or oxidative stress. Protein aggregation and inclusions are hallmarks of a number of neurodegenerative diseases. Recent evidence that links protein aggregation to oxidative stress and mitochondrial dysfunction will also be examined. Lastly, current therapies that target mitochondrial dysfunction or oxidative stress are discussed.

Role of the basal ganglia in category learning: how do patients with Parkinson's disease learn?

The purpose of the present study was to gain a deeper understanding of the role of the basal ganglia in learning and memory by examining learning strategies among patients with basal ganglia dysfunction. Using a probabilistic category learning task (the "weather prediction" task) previously shown to be sensitive to basal ganglia function, the authors examined patterns of performance during learning and used mathematical models to capture different learning strategies. Results showed that patients with Parkinson's disease exhibit different patterns of strategy use. Specifically, most controls initially used a simple, but suboptimal, strategy that focused on single-cue-outcome associations; eventually, however, most controls adopted a more complex, optimal learning strategy, integrating single-cue associations to predict outcomes for multiple-cue stimuli. In contrast, the majority of individuals with Parkinson's disease continued to rely on simple single-cue learning strategies throughout the experiment.

Novel dopamine releasing response of an anti-convulsant agent with possible anti-Parkinson's activity.

We used cerebral microdialysis to assess the ability of the anticonvulsant drug Zonisamide (ZNS) to release striatal dopamine in 6-hydroxydopamine nigrotomized rats. Following exogeneously administered ZNS we measured dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in striatal dialysates obtained from the ipsilateral side of the nigrotomy. ZNS administration alone had no effect on levels of DA and its metabolites or rotational behavior. Administration of carbidopa-levodopa alone led to small but insignificant increases in rotational behavior contralateral to the side of the nigrotomy but no corresponding increases in indices of striatal catecholamine release. In contrast, if animals were preloaded with carbidopa and ZNS was co-administered with levodopa 30 minutes later significant increases in contralateral rotational behavior occurred within 20 minutes of ZNS-levodopa injection that lasted for at least 90 minutes. In contrast to the uniform rotational behavioral responses observed in all our nigrotomized animals, less than half demonstrated neurochemical evidence of DA release. In these "responder" animals DOPAC levels increased 300% following carbidopa-levodopa-ZNS administration. We conclude that these results support previously reported findings and provide additional evidence that the anticonvulsant ZNS appears to possess anti-Parkinson's properties. ZNS could therefore be a novel agent for the treatment of PD that could delay the use of or reduce the amount of levodopa needed to treat patients with PD.

Cortico-striatal contributions to feedback-based learning: converging data from neuroimaging and neuropsychology.

The striatum has been widely implicated in cognition, but a precise understanding of its role remains elusive. Here we present converging evidence for the role of the striatum in feedback-based learning. In a prior functional imaging study, healthy controls showed striatal activity during a feedback-based learning task, which was decreased when the same task was learned without feedback. In the present study, we show that individuals with striatal dysfunction due to Parkinson's disease are impaired on the feedback-based task, but not on a non-feedback version of the same task. Parkinson's patients and controls also used different learning strategies depending on feedback structure. This study provides direct behavioural evidence from humans that cortico-striatal systems are necessary for feedback-based learning on a cognitive task. These findings also link between learning impairments in Parkinson's disease and the physiological and computational evidence for the role of midbrain dopaminergic systems in feedback processing.

Human midbrain sensitivity to cognitive feedback and uncertainty during classification learning.

Mesencephalic dopaminergic system (MDS) neurons may participate in learning by providing a prediction error signal to their targets, which include ventral striatal, orbital, and medial frontal regions, as well as by showing sensitivity to the degree of uncertainty associated with individual stimuli. We investigated the mechanisms of probabilistic classification learning in humans using functional magnetic resonance imaging to examine the effects of feedback and uncertainty. The design was optimized for separating neural responses to stimulus, delay, and negative and positive feedback components. Compared with fixation, stimulus and feedback activated brain regions consistent with the MDS, whereas the delay period did not. Midbrain activity was significantly different for negative versus positive feedback (consistent with coding of the "prediction error") and was reliably correlated with the degree of uncertainty as well as with activity in MDS target regions. Purely cognitive feedback apparently engages the same regions as rewarding stimuli, consistent with a broader characterization of this network.