Low Thalamic NAA-Concentration Corresponds to Strong Neural Activation in Working Memory in Kleine-Levin Syndrome

Background

Kleine Levin Syndrome (KLS) is a rare disorder of periodic hypersomnia and behavioural disturbances in young individuals. It has previously been shown to be associated with disturbances of working memory (WM), which, in turn, was associated with higher activation of the thalamus with increasing WM load, demonstrated with functional magnetic resonance imaging (fMRI). In this study we aimed to further elucidate how these findings are related to the metabolism of the thalamus.

Methods

fMRI and magnetic resonance spectroscopy were applied while performing a WM task. Standard metabolites were examined: n-acetylaspartate (NAA), myo-inositol, choline, creatine and glutamate-glutamine. Fourteen KLS-patients and 15 healthy controls participated in the study. The patients with active disease were examined in asymptomatic periods.

Results

There was a statistically significant negative correlation between thalamic fMRI-activation and thalamic NAA, i.e., high fMRI-activation corresponded to low NAA-levels. This correlation was not seen in healthy controls. Thalamic levels of NAA in patients and controls showed no significant differences between the groups. None of the other metabolites showed any co-variation with fMRI-activiation.

Conclusion

This study shows negative correlation between NAA-levels and fMRI-activity in the left thalamus of KLS-patients while performing a WM task. This correlation could not be found in healthy control subjects, primarily interpreted as an effect of increased effort in the patient group upon performing the task. It might indicate a disturbance in the neuronal networks responsible for WM in KLS patients, resulting in higher effort at lower WM load, compared with healthy subjects. The general relationship between NAA and BOLD-signal is also discussed in the article.     

Khat use is associated with impaired working memory and cognitive flexibility

Rationale

Khat consumption has increased during the last decades in Eastern Africa and has become a global phenomenon spreading to ethnic communities in the rest of the world, such as The Netherlands, United Kingdom, Canada, and the United States. Very little is known, however, about the relation between khat use and cognitive control functions in khat users.

Objective

We studied whether khat use is associated with changes in working memory (WM) and cognitive flexibility, two central cognitive control functions.

Methods

Khat users and khat-free controls were matched in terms of sex, ethnicity, age, alcohol and cannabis consumption, and IQ (Raven''s progressive matrices). Groups were tested on cognitive flexibility, as measured by a Global-Local task, and on WM using an N-back task.

Result

Khat users performed significantly worse than controls on tasks tapping into cognitive flexibility as well as monitoring of information in WM.

Conclusions

The present findings suggest that khat use impairs both cognitive flexibility and the updating of information in WM. The inability to monitor information in WM and to adjust behavior rapidly and flexibly may have repercussions for daily life activities.     

Simultaneous EEG-fMRI during a Working Memory Task: Modulations in Low and High Frequency Bands

Background

EEG studies of working memory (WM) have demonstrated load dependent frequency band modulations. FMRI studies have localized load modulated activity to the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and posterior parietal cortex (PPC). Recently, an EEG-fMRI study found that low frequency band (theta and alpha) activity negatively correlated with the BOLD signal during the retention phase of a WM task. However, the coupling of higher (beta and gamma) frequencies with the BOLD signal during WM is unknown.

Methodology

In 16 healthy adult subjects, we first investigated EEG-BOLD signal correlations for theta (5–7 Hz), alpha1 (8–10), alpha2 (10–12 Hz), beta1 (13–20), beta2 (20–30 Hz), and gamma (30–40 Hz) during the retention period of a WM task with set size 2 and 5. Secondly, we investigated whether load sensitive brain regions are characterised by effects that relate frequency bands to BOLD signals effects.

Principal Findings

We found negative theta-BOLD signal correlations in the MPFC, PPC, and cingulate cortex (ACC and PCC). For alpha1 positive correlations with the BOLD signal were found in ACC, MPFC, and PCC; negative correlations were observed in DLPFC, PPC, and inferior frontal gyrus (IFG). Negative alpha2-BOLD signal correlations were observed in parieto-occipital regions. Beta1-BOLD signal correlations were positive in ACC and negative in precentral and superior temporal gyrus. Beta2 and gamma showed only positive correlations with BOLD, e.g., in DLPFC, MPFC (gamma) and IFG (beta2/gamma). The load analysis revealed that theta and—with one exception—beta and gamma demonstrated exclusively positive load effects, while alpha1 showed only negative effects.

Conclusions

We conclude that the directions of EEG-BOLD signal correlations vary across brain regions and EEG frequency bands. In addition, some brain regions show both load sensitive BOLD and frequency band effects. Our data indicate that lower as well as higher frequency brain oscillations are linked to neurovascular processes during WM.     

The effect of repetitive transcranial magnetic stimulation on gamma oscillatory activity in schizophrenia

Background

Gamma (γ) oscillations (30–50 Hz) have been shown to be excessive in patients with schizophrenia (SCZ) during working memory (WM). WM is a cognitive process that involves the online maintenance and manipulation of information that is mediated largely by the dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS) represents a non-invasive method to stimulate the cortex that has been shown to enhance cognition and γ oscillatory activity during WM.

Methodology and Principal Findings

We examined the effect of 20 Hz rTMS over the DLPFC on γ oscillatory activity elicited during the N-back task in 24 patients with SCZ compared to 22 healthy subjects. Prior to rTMS, patients with SCZ elicited excessive γ oscillatory activity compared to healthy subjects across WM load. Active rTMS resulted in the reduction of frontal γ oscillatory activity in patients with SCZ, while potentiating activity in healthy subjects in the 3-back, the most difficult condition. Further, these effects on γ oscillatory activity were found to be specific to the frontal brain region and were absent in the parieto-occipital brain region.

Conclusions and Significance

We suggest that this opposing effect of rTMS on γ oscillatory activity in patients with SCZ versus healthy subjects may be related to homeostatic plasticity leading to differential effects of rTMS on γ oscillatory activity depending on baseline differences. These findings provide important insights into the neurophysiological mechanisms underlying WM deficits in SCZ and demonstrated that rTMS can modulate γ oscillatory activity that may be a possible avenue for cognitive potentiation in this disorder.     

The Effects of Valence and Arousal on Associative Working Memory and Long-Term Memory

Background

Emotion can either facilitate or impair memory, depending on what, when and how memory is tested and whether the paradigm at hand is administered as a working memory (WM) or a long-term memory (LTM) task. Whereas emotionally arousing single stimuli are more likely to be remembered, memory for the relationship between two or more component parts (i.e., relational memory) appears to be worse in the presence of emotional stimuli, at least in some relational memory tasks. The current study investigated the effects of both valence (neutral vs. positive vs. negative) and arousal (low vs. high) in an inter-item WM binding and LTM task.

Methodology/Principal Findings

A five-pair delayed-match-to-sample (WM) task was administered. In each trial, study pairs consisted of one neutral picture and a second picture of which the emotional qualities (valence and arousal levels) were manipulated. These pairs had to be remembered across a delay interval of 10 seconds. This was followed by a probe phase in which five pairs were tested. After completion of this task, an unexpected single item LTM task as well as an LTM task for the pairs was assessed. As expected, emotional arousal impaired WM processing. This was reflected in lower accuracy for pairs consisting of high-arousal pictures compared to pairs with low-arousal pictures. A similar effect was found for the associative LTM task. However, the arousal effect was modulated by affective valence for the WM but not the LTM task; pairs with low-arousal negative pictures were not processed as well in the WM task. No significant differences were found for the single-item LTM task.

Conclusions/Significance

The present study provides additional evidence that processes during initial perception/encoding and post-encoding processes, the time interval between study and test and the interaction between valence and arousal might modulate the effects of “emotion” on associative memory.     

The impact of anxiety-inducing distraction on cognitive performance: a combined brain imaging and personality investigation

Background

Previous investigations revealed that the impact of task-irrelevant emotional distraction on ongoing goal-oriented cognitive processing is linked to opposite patterns of activation in emotional and perceptual vs. cognitive control/executive brain regions. However, little is known about the role of individual variations in these responses. The present study investigated the effect of trait anxiety on the neural responses mediating the impact of transient anxiety-inducing task-irrelevant distraction on cognitive performance, and on the neural correlates of coping with such distraction. We investigated whether activity in the brain regions sensitive to emotional distraction would show dissociable patterns of co-variation with measures indexing individual variations in trait anxiety and cognitive performance.

Methodology/Principal Findings

Event-related fMRI data, recorded while healthy female participants performed a delayed-response working memory (WM) task with distraction, were investigated in conjunction with behavioural measures that assessed individual variations in both trait anxiety and WM performance. Consistent with increased sensitivity to emotional cues in high anxiety, specific perceptual areas (fusiform gyrus - FG) exhibited increased activity that was positively correlated with trait anxiety and negatively correlated with WM performance, whereas specific executive regions (right lateral prefrontal cortex - PFC) exhibited decreased activity that was negatively correlated with trait anxiety. The study also identified a role of the medial and left lateral PFC in coping with distraction, as opposed to reflecting a detrimental impact of emotional distraction.

Conclusions

These findings provide initial evidence concerning the neural mechanisms sensitive to individual variations in trait anxiety and WM performance, which dissociate the detrimental impact of emotion distraction and the engagement of mechanisms to cope with distracting emotions. Our study sheds light on the neural correlates of emotion-cognition interactions in normal behaviour, which has implications for understanding factors that may influence susceptibility to affective disorders, in general, and to anxiety disorders, in particular.     

The Relationship between Visual-Spatial and Auditory-Verbal Working Memory Span in Senegalese and Ugandan Children

Background

Using the Kaufman Assessment Battery for Children (K-ABC) Conant et al. (1999) observed that visual and auditory working memory (WM) span were independent in both younger and older children from DR Congo, but related in older American children and in Lao children [1]. The present study evaluated whether visual and auditory WM span were independent in Ugandan and Senegalese children.

Method

In a linear regression analysis we used visual (Spatial Memory, Hand Movements) and auditory (Number Recall) WM along with education and physical development (weight/height) as predictors. The predicted variable in this analysis was Word Order, which is a verbal memory task that has both visual and auditory memory components.

Results

Both the younger (<8.5 yrs) and older (>8.5 yrs) Ugandan children had auditory memory span (Number Recall) that was strongly predictive of Word Order performance. For both the younger and older groups of Senegalese children, only visual WM span (Spatial Memory) was strongly predictive of Word Order. Number Recall was not significantly predictive of Word Order in either age group.

Conclusions

It is possible that greater literacy from more schooling for the Ugandan age groups mediated their greater degree of interdependence between auditory and verbal WM. Our findings support those of Conant et al., who observed in their cross-cultural comparisons that stronger education seemed to enhance the dominance of the phonological-auditory processing loop for WM.     

Anatomical Abnormalities in Gray and White Matter of the Cortical Surface in Persons with Schizophrenia

Background

Although schizophrenia has been associated with abnormalities in brain anatomy, imaging studies have not fully determined the nature and relative contributions of gray matter (GM) and white matter (WM) disturbances underlying these findings. We sought to determine the pattern and distribution of these GM and WM abnormalities. Furthermore, we aimed to clarify the contribution of abnormalities in cortical thickness and cortical surface area to the reduced GM volumes reported in schizophrenia.

Methods

We recruited 76 persons with schizophrenia and 57 healthy controls from the community and obtained measures of cortical and WM surface areas, of local volumes along the brain and WM surfaces, and of cortical thickness.

Results

We detected reduced local volumes in patients along corresponding locations of the brain and WM surfaces in addition to bilateral greater thickness of perisylvian cortices and thinner cortex in the superior frontal and cingulate gyri. Total cortical and WM surface areas were reduced. Patients with worse performance on the serial-position task, a measure of working memory, had a higher burden of WM abnormalities.

Conclusions

Reduced local volumes along the surface of the brain mirrored the locations of abnormalities along the surface of the underlying WM, rather than of abnormalities of cortical thickness. Moreover, anatomical features of white matter, but not cortical thickness, correlated with measures of working memory. We propose that reductions in WM and smaller total cortical surface area could be central anatomical abnormalities in schizophrenia, driving, at least partially, the reduced regional GM volumes often observed in this illness.     

Dopamine Transporters in Striatum Correlate with Deactivation in the Default Mode Network during Visuospatial Attention

Background

Dopamine and dopamine transporters (DAT, which regulate extracellular dopamine in the brain) are implicated in the modulation of attention but their specific roles are not well understood. Here we hypothesized that dopamine modulates attention by facilitation of brain deactivation in the default mode network (DMN). Thus, higher striatal DAT levels, which would result in an enhanced clearance of dopamine and hence weaker dopamine signals, would be associated to lower deactivation in the DMN during an attention task.

Methodology/Principal Findings

For this purpose we assessed the relationship between DAT in striatum (measured with positron emission tomography and [¹¹C]cocaine used as DAT radiotracer) and brain activation and deactivation during a parametric visual attention task (measured with blood oxygenation level dependent functional magnetic resonance imaging) in healthy controls. We show that DAT availability in caudate and putamen had a negative correlation with deactivation in ventral parietal regions of the DMN (precuneus, BA 7) and a positive correlation with deactivation in a small region in the ventral anterior cingulate gyrus (BA 24/32). With increasing attentional load, DAT in caudate showed a negative correlation with load-related deactivation increases in precuneus.

Conclusions/Significance

These findings provide evidence that dopamine transporters modulate neural activity in the DMN and anterior cingulate gyrus during visuospatial attention. Our findings suggest that dopamine modulates attention in part by regulating neuronal activity in posterior parietal cortex including precuneus (region involved in alertness) and cingulate gyrus (region deactivated in proportion to emotional interference). These findings suggest that the beneficial effects of stimulant medications (increase dopamine by blocking DAT) in inattention reflect in part their ability to facilitate the deactivation of the DMN.     

Resting-State Neuronal Oscillatory Correlates of Working Memory Performance

Purpose

Working memory (WM) represents the brain’s ability to maintain information in a readily available state for short periods of time. This study examines the resting-state cortical activity patterns that are most associated with performance on a difficult working-memory task.

Methods

Magnetoencephalographic (MEG) band-passed (delta/theta (1–7 Hz), alpha (8–13 Hz), beta (14–30 Hz)) and sensor based regional power was collected in a population of adult men (18–28 yrs, n = 24) in both an eyes-closed and eyes-open resting state. The normalized power within each resting state condition as well as the normalized change in power between eyes closed and open (zECO) were correlated with performance on a WM task. The regional and band-limited measures that were most associated with performance were then combined using singular value decomposition (SVD) to determine the degree to which zECO power was associated with performance on the three-back verbal WM task.

Results

Changes in power from eyes closed to open revealed a significant decrease in power in all band-widths that was most pronounced in the posterior brain regions (delta/theta band). zECO right posterior frontal and parietal cortex delta/theta power were found to be inversely correlated with three-back working memory performance. The SVD evaluation of the most correlated zECO metrics then provided a singular measure that was highly correlated with three-back performance (r = −0.73, p<0.0001).

Conclusion

Our results indicate that there is an association between WM performance and changes in resting-state power (right posterior frontal and parietal delta/theta power). Moreover, an SVD of the most associated zECO measures produces a composite resting-state metric of regional neural oscillatory power that has an improved association with WM performance. To our knowledge, this is the first investigation that has found that changes in resting state electromagnetic neural patterns are highly associated with verbal working memory performance.     

Risk Factors for Treatment Default among Re-Treatment Tuberculosis Patients in India, 2006

Setting

Under India''s Revised National Tuberculosis Control Programme (RNTCP), >15% of previously-treated patients in the reported 2006 patient cohort defaulted from anti-tuberculosis treatment.

Objective

To assess the timing, characteristics, and risk factors for default amongst re-treatment TB patients.

Methodology

For this case-control study, in 90 randomly-selected programme units treatment records were abstracted from all 2006 defaulters from the RNTCP re-treatment regimen (cases), with one consecutively-selected non-defaulter per case. Patients who interrupted anti-tuberculosis treatment for >2 months were classified as defaulters.

Results

1,141 defaulters and 1,189 non-defaulters were included. The median duration of treatment prior to default was 81 days (25%–75% interquartile range 44–117 days) and documented retrieval efforts after treatment interruption were inadequate. Defaulters were more likely to have been male (adjusted odds ratio [aOR] 1.4, 95% confidence interval [CI] 1.2–1.7), have previously defaulted anti-tuberculosis treatment (aOR 1.3 95%CI 1.1–1.6], have previous treatment from non-RNTCP providers (AOR 1.3, 95%CI 1.0–1.6], or have public health facility-based treatment observation (aOR 1.3, 95%CI 1.1–1.6).

Conclusions

Amongst the large number of re-treatment patients in India, default occurs early and often. Improved pre-treatment counseling and community-based treatment provision may reduce default rates. Efforts to retrieve treatment interrupters prior to default require strengthening.     

Anterior medial prefrontal cortex exhibits activation during task preparation but deactivation during task execution

Background

The anterior prefrontal cortex (PFC) exhibits activation during some cognitive tasks, including episodic memory, reasoning, attention, multitasking, task sets, decision making, mentalizing, and processing of self-referenced information. However, the medial part of anterior PFC is part of the default mode network (DMN), which shows deactivation during various goal-directed cognitive tasks compared to a resting baseline. One possible factor for this pattern is that activity in the anterior medial PFC (MPFC) is affected by dynamic allocation of attentional resources depending on task demands. We investigated this possibility using an event related fMRI with a face working memory task.

Methodology/Principal Findings

Sixteen students participated in a single fMRI session. They were asked to form a task set to remember the faces (Face memory condition) or to ignore them (No face memory condition), then they were given 6 seconds of preparation period before the onset of the face stimuli. During this 6-second period, four single digits were presented one at a time at the center of the display, and participants were asked to add them and to remember the final answer. When participants formed a task set to remember faces, the anterior MPFC exhibited activation during a task preparation period but deactivation during a task execution period within a single trial.

Conclusions/Significance

The results suggest that the anterior MPFC plays a role in task set formation but is not involved in execution of the face working memory task. Therefore, when attentional resources are allocated to other brain regions during task execution, the anterior MPFC shows deactivation. The results suggest that activation and deactivation in the anterior MPFC are affected by dynamic allocation of processing resources across different phases of processing.     

Altered Topological Organization of White Matter Structural Networks in Patients with Neuromyelitis Optica

Objective

To investigate the topological alterations of the whole-brain white-matter (WM) structural networks in patients with neuromyelitis optica (NMO).

Methods

The present study involved 26 NMO patients and 26 age- and sex-matched healthy controls. WM structural connectivity in each participant was imaged with diffusion-weighted MRI and represented in terms of a connectivity matrix using deterministic tractography method. Graph theory-based analyses were then performed for the characterization of brain network properties. A multiple linear regression analysis was performed on each network metric between the NMO and control groups.

Results

The NMO patients exhibited abnormal small-world network properties, as indicated by increased normalized characteristic path length, increased normalized clustering and increased small-worldness. Furthermore, largely similar hub distributions of the WM structural networks were observed between NMO patients and healthy controls. However, regional efficiency in several brain areas of NMO patients was significantly reduced, which were mainly distributed in the default-mode, sensorimotor and visual systems. Furthermore, we have observed increased regional efficiency in a few brain regions such as the orbital parts of the superior and middle frontal and fusiform gyri.

Conclusion

Although the NMO patients in this study had no discernible white matter T2 lesions in the brain, we hypothesize that the disrupted topological organization of WM networks provides additional evidence for subtle, widespread cerebral WM pathology in NMO.     

The Default Mode Network and the Working Memory Network Are Not Anti-Correlated during All Phases of a Working Memory Task

Introduction

The default mode network and the working memory network are known to be anti-correlated during sustained cognitive processing, in a load-dependent manner. We hypothesized that functional connectivity among nodes of the two networks could be dynamically modulated by task phases across time.

Methods

To address the dynamic links between default mode network and the working memory network, we used a delayed visuo-spatial working memory paradigm, which allowed us to separate three different phases of working memory (encoding, maintenance, and retrieval), and analyzed the functional connectivity during each phase within and between the default mode network and the working memory network networks.

Results

We found that the two networks are anti-correlated only during the maintenance phase of working memory, i.e. when attention is focused on a memorized stimulus in the absence of external input. Conversely, during the encoding and retrieval phases, when the external stimulation is present, the default mode network is positively coupled with the working memory network, suggesting the existence of a dynamically switching of functional connectivity between “task-positive” and “task-negative” brain networks.

Conclusions

Our results demonstrate that the well-established dichotomy of the human brain (anti-correlated networks during rest and balanced activation-deactivation during cognition) has a more nuanced organization than previously thought and engages in different patterns of correlation and anti-correlation during specific sub-phases of a cognitive task. This nuanced organization reinforces the hypothesis of a direct involvement of the default mode network in cognitive functions, as represented by a dynamic rather than static interaction with specific task-positive networks, such as the working memory network.     

Focusing on attention: the effects of working memory capacity and load on selective attention

Background

Working memory (WM) is imperative for effective selective attention. Distractibility is greater under conditions of high (vs. low) concurrent working memory load (WML), and in individuals with low (vs. high) working memory capacity (WMC). In the current experiments, we recorded the flanker task performance of individuals with high and low WMC during low and high WML, to investigate the combined effect of WML and WMC on selective attention.

Methodology/Principal Findings

In Experiment 1, distractibility from a distractor at a fixed distance from the target was greater when either WML was high or WMC was low, but surprisingly smaller when both WML was high and WMC low. Thus we observed an inverted-U relationship between reductions in WM resources and distractibility. In Experiment 2, we mapped the distribution of spatial attention as a function of WMC and WML, by recording distractibility across several target-to-distractor distances. The pattern of distractor effects across the target-to-distractor distances demonstrated that the distribution of the attentional window becomes dispersed as WM resources are limited. The attentional window was more spread out under high compared to low WML, and for low compared to high WMC individuals, and even more so when the two factors co-occurred (i.e., under high WML in low WMC individuals). The inverted-U pattern of distractibility effects in Experiment 1, replicated in Experiment 2, can thus be explained by differences in the spread of the attentional window as a function of WM resource availability.

Conclusions/Significance

The current findings show that limitations in WM resources, due to either WML or individual differences in WMC, affect the spatial distribution of attention. The difference in attentional constraining between high and low WMC individuals demonstrated in the current experiments helps characterise the nature of previously established associations between WMC and controlled attention.     

Intake of green tea inhibited increase of salivary chromogranin A after mental task stress loads

Background

Green tea has become renowned for its health benefits. In this study, we investigated the anti-stress effect of two kinds of green tea against a mental stress task load.

Methods

Warm water, ordinary green tea (Sagara), and shaded white tea, which contains more amino acid components than Sagara, were used as test samples in a randomized cross-over design study. Eighteen students (nine male and nine female) participated in three experimental trials on different days at intervals of seven days. Saliva was collected before beverage intake and after performing the mental stress load tasks. Concentration of chromogranin A (CgA) in the saliva was used as an index of autonomic nervous system activity.

Results

CgA level increased after the mental tasks, but intake of green tea inhibited this increase; the anti-stress effect was even greater after consumption of shaded white tea. Intake of shaded white tea also lowered Total Mood Disturbance (TMD) score on the Profile of Mood States (POMS); subjects in this condition tended to perform more calculations in the arithmetic task than those in the warm water treatment condition.

Conclusions

Salivary CgA concentration levels increased after mental stress load tasks, but ingestion of green tea inhibited this increase. This anti-stress effect was larger after the consumption of shaded white tea than after Sagara. Shaded white tea intake also lowered TMD score (POMS) and tended to improve performance on an arithmetic task compared to warm water, suggesting that shaded white tea might also improve mood during and after mental stress load.     

A Consistency-Based Feature Selection Method Allied with Linear SVMs for HIV-1 Protease Cleavage Site Prediction

Background

Predicting type-1 Human Immunodeficiency Virus (HIV-1) protease cleavage site in protein molecules and determining its specificity is an important task which has attracted considerable attention in the research community. Achievements in this area are expected to result in effective drug design (especially for HIV-1 protease inhibitors) against this life-threatening virus. However, some drawbacks (like the shortage of the available training data and the high dimensionality of the feature space) turn this task into a difficult classification problem. Thus, various machine learning techniques, and specifically several classification methods have been proposed in order to increase the accuracy of the classification model. In addition, for several classification problems, which are characterized by having few samples and many features, selecting the most relevant features is a major factor for increasing classification accuracy.

Results

We propose for HIV-1 data a consistency-based feature selection approach in conjunction with recursive feature elimination of support vector machines (SVMs). We used various classifiers for evaluating the results obtained from the feature selection process. We further demonstrated the effectiveness of our proposed method by comparing it with a state-of-the-art feature selection method applied on HIV-1 data, and we evaluated the reported results based on attributes which have been selected from different combinations.

Conclusion

Applying feature selection on training data before realizing the classification task seems to be a reasonable data-mining process when working with types of data similar to HIV-1. On HIV-1 data, some feature selection or extraction operations in conjunction with different classifiers have been tested and noteworthy outcomes have been reported. These facts motivate for the work presented in this paper.

Software availability

The software is available at http://ozyer.etu.edu.tr/c-fs-svm.rar.The software can be downloaded at esnag.etu.edu.tr/software/hiv_cleavage_site_prediction.rar; you will find a readme file which explains how to set the software in order to work.     

Default Network Deactivations Are Correlated with Psychopathic Personality Traits

Background

The posteromedial cortex (PMC) and medial prefrontal cortex (mPFC) are part of a network of brain regions that has been found to exhibit decreased activity during goal-oriented tasks. This network is thought to support a baseline of brain activity, and is commonly referred to as the “default network”. Although recent reports suggest that the PMC and mPFC are associated with affective, social, and self-referential processes, the relationship between these default network components and personality traits, especially those pertaining to social context, is poorly understood.

Methodology/Principal Findings

In the current investigation, we assessed the relationship between PMC and mPFC deactivations and psychopathic personality traits using fMRI and a self-report measure. We found that PMC deactivations predicted traits related to egocentricity and mPFC deactivations predicted traits related to decision-making.

Conclusions/Significance

These results suggest that the PMC and mPFC are associated with processes involving self-relevancy and affective decision-making, consistent with previous reports. More generally, these findings suggest a link between default network activity and personality traits.     

Treatment Default amongst Patients with Tuberculosis in Urban Morocco: Predicting and Explaining Default and Post-Default Sputum Smear and Drug Susceptibility Results

Setting

Public tuberculosis (TB) clinics in urban Morocco.

Objective

Explore risk factors for TB treatment default and develop a prediction tool. Assess consequences of default, specifically risk for transmission or development of drug resistance.

Design

Case-control study comparing patients who defaulted from TB treatment and patients who completed it using quantitative methods and open-ended questions. Results were interpreted in light of health professionals’ perspectives from a parallel study. A predictive model and simple tool to identify patients at high risk of default were developed. Sputum from cases with pulmonary TB was collected for smear and drug susceptibility testing.

Results

91 cases and 186 controls enrolled. Independent risk factors for default included current smoking, retreatment, work interference with adherence, daily directly observed therapy, side effects, quick symptom resolution, and not knowing one’s treatment duration. Age >50 years, never smoking, and having friends who knew one’s diagnosis were protective. A simple scoring tool incorporating these factors was 82.4% sensitive and 87.6% specific for predicting default in this population. Clinicians and patients described additional contributors to default and suggested locally-relevant intervention targets. Among 89 cases with pulmonary TB, 71% had sputum that was smear positive for TB. Drug resistance was rare.

Conclusion

The causes of default from TB treatment were explored through synthesis of qualitative and quantitative data from patients and health professionals. A scoring tool with high sensitivity and specificity to predict default was developed. Prospective evaluation of this tool coupled with targeted interventions based on our findings is warranted. Of note, the risk of TB transmission from patients who default treatment to others is likely to be high. The commonly-feared risk of drug resistance, though, may be low; a larger study is required to confirm these findings.     

Nicotinic receptor gene CHRNA4 interacts with processing load in attention

Background

Pharmacological studies suggest that cholinergic neurotransmission mediates increases in attentional effort in response to high processing load during attention demanding tasks [1].

Methodology/Principal Findings

In the present study we tested whether individual variation in CHRNA4, a gene coding for a subcomponent in α4β2 nicotinic receptors in the human brain, interacted with processing load in multiple-object tracking (MOT) and visual search (VS). We hypothesized that the impact of genotype would increase with greater processing load in the MOT task. Similarly, we predicted that genotype would influence performance under high but not low load in the VS task. Two hundred and two healthy persons (age range = 39–77, Mean = 57.5, SD = 9.4) performed the MOT task in which twelve identical circular objects moved about the display in an independent and unpredictable manner. Two to six objects were designated as targets and the remaining objects were distracters. The same observers also performed a visual search for a target letter (i.e. X or Z) presented together with five non-targets while ignoring centrally presented distracters (i.e. X, Z, or L). Targets differed from non-targets by a unique feature in the low load condition, whereas they shared features in the high load condition. CHRNA4 genotype interacted with processing load in both tasks. Homozygotes for the T allele (N = 62) had better tracking capacity in the MOT task and identified targets faster in the high load trials of the VS task.

Conclusion

The results support the hypothesis that the cholinergic system modulates attentional effort, and that common genetic variation can be used to study the molecular biology of cognition.