Trade-off between capacity and precision in visuospatial working memory.

Limitations in the performance of working memory (WM) tasks have been characterized in terms of the number of items retained (capacity) and in terms of the precision with which the information is retained. The neural mechanisms behind these limitations are still unclear. Here we used a biological constrained computational model to study the capacity and precision of visuospatial WM. The model consists of two connected networks of spiking neurons. One network is responsible for storage of information. The other provides a nonselective excitatory input to the storage network. Simulations showed that this excitation boost could temporarily increase storage capacity but also predicted that this would be associated with a decrease in precision of the memory. This prediction was subsequently tested in a behavioral (38 participants) and fMRI (22 participants) experiment. The behavioral results confirmed the trade-off effect, and the fMRI results suggest that a frontal region might be engaged in the trial-by-trial control of WM performance. The average effects were small, but individuals differed in the amount of trade-off, and these differences correlated with the frontal activation. These results support a two-module model of WM where performance is determined both by storage capacity and by top-down influence, which can vary on a trial-by-trial basis, affecting both the capacity and precision of WM.

Stages of nonsymbolic number processing in occipitoparietal cortex disentangled by fMRI adaptation.

The neurobiological mechanisms of nonsymbolic number processing in humans are still unclear. Computational modeling proposed three successive stages: first, the spatial location of objects is stored in an object location map; second, this information is transformed into a numerical summation code; third, this summation code is transformed to a number-selective code. Here, we used fMRI-adaptation to identify these three stages and their relative anatomical location. By presenting the same number of dots on the same locations in the visual field, we adapted neurons of human volunteers. Occasionally, deviants with the same number of dots at different locations or different numbers of dots at the same location were shown. By orthogonal number and location factors in the deviants, we were able to calculate three independent contrasts, each sensitive to one of the stages. We found an occipitoparietal gradient for nonsymbolic number processing: the activation of the object location map was found in the inferior occipital gyrus. The summation coding map exhibited a nonlinear pattern of activation, with first increasing and then decreasing activation, and most activity in the middle occipital gyrus. Finally, the number-selective code became more pronounced in the superior parietal lobe. In summary, we disentangled the three stages of nonsymbolic number processing predicted by computational modeling and demonstrated that they constitute a pathway along the occipitoparietal processing stream.

Number processing pathways in human parietal cortex.

Numerous studies have identified the intraparietal sulcus (IPS) as an area critically involved in numerical processing. IPS neurons in macaques are tuned to a preferred numerosity, hence neurally coding numerosity in a number-selective way. Neuroimaging studies in humans have demonstrated number-selective processing in the anterior parts of the IPS. Nevertheless, the processes that convert visual input into a number-selective neural code remain unknown. Computational studies have suggested that a neural coding stage that is sensitive, but not selective to number, precedes number-selective coding when processing nonsymbolic quantities but not when processing symbolic quantities. In Experiment 1, we used functional magnetic resonance imaging to localize number-sensitive areas in the human brain by searching for areas exhibiting increasing activation with increasing number, carefully controlling for nonnumerical parameters. An area in posterior superior parietal cortex was identified as a substrate for the intermediate number-sensitive steps required for processing nonsymbolic quantities. In Experiment 2, the interpretation of Experiment 1 was confirmed with a connectivity analysis showing that a shared number-selective representation in IPS is reached through different pathways for symbolic versus nonsymbolic quantities. The preferred pathway for processing nonsymbolic quantities included the number-sensitive area in superior parietal cortex, whereas the pathway for processing symbolic quantities did not.

Salience maps in parietal cortex: imaging and computational modeling.

Models of spatial attention are often based on the concept of a salience map. In computational cognitive neuroscience, such maps are implemented as a collection of nodes with self-excitation and lateral inhibition between all nodes (competitive interaction map). Here, we test some critical predictions of this idea. We argued that task demands, more precisely the level of attention required, can top-down modulate the level of lateral inhibition in a salience map, and thus induce different activation functions. We first show that a model with a high lateral inhibition parameter generates a monotonous activation curve as a function of set size similar to that typically observed in the literature (e.g. Todd and Marois, 2004). Next, we show that a competitive interaction map with medium lateral inhibition leads to a Lambda-shaped activation curve when set sizes increase. This prediction is confirmed in an fMRI experiment with medium attention demands where a similar Lambda-shaped activation curve is found in a posterior superior parietal area that was proposed to house a salience map (Todd and Marois, 2004). Finally, we show that a qualitatively different V-shaped activation curve is predicted with a very low inhibition parameter. An fMRI experiment with low attentional demands revealed this V-shaped activation curve in the same region. These findings provide critical support for the existence of a salience map based on competitive interactions in posterior superior parietal cortex, and suggest that its parameters (in particular, lateral inhibition) can be modulated in a top down manner dependent on task demands.

Hippocampal contribution to early and later stages of implicit motor sequence learning.

Implicit motor sequence learning refers to an important human ability to acquire new motor skills through the repeated performance of a motor sequence. This learning process is characterized by slow, incremental gains of motor performance. The present fMRI study was developed to better delineate the areas supporting these temporal dynamics of learning. By using the serial color matching paradigm, our study focused on the motor level of sequence learning and tracked the time course of learning-related neural changes. Imaging results showed a significant contribution of the left anterior hippocampus in an early sequence acquisition stage (first scanning session) as well as during a later stage with stabilized learning effects (second scanning session). Hippocampal activation significantly correlated with the behavioral learning process and was affected by a change of the motor sequence. These results suggest a strong involvement of the hippocampus in implicit motor sequence learning. On the other hand, a very extensive and bilateral neural network of parietal, temporal and frontal cortical areas (including SMA, pre-SMA) together with parts of the cerebellum and striatum were found to play a role during random visuo-motor task performance.

Association Between Nursing Support Levels and Effectiveness of Golimumab in the Management of Patients with Rheumatologic Diseases.

INTRODUCTION: The main objective of this study was to assess the level of nursing support received by biologic-naïve rheumatological patients treated with golimumab during their first cycle. METHODS: Adult patients (N = 119; aged 46.9 ± 13.4 years (mean ± standard deviation); 49.6% males), with rheumatoid arthritis (N = 40), ankylosing spondylitis (N = 58) or psoriatic arthritis (N = 21), and treated with golimumab (first tumor necrosis factor-α inhibitor) during a first reimbursement cycle were included by 17 Belgian centers. Patients were categorized in three levels of nursing support (intense, medium, or low). They filled in a non-validated and exploratory questionnaire about satisfaction, quality, and helpfulness of information. RESULTS: The nursing support was considered intense, medium, or low for 98 (82.4%), 10 (8.4%), and 11 (9.2%) patients, respectively. All disease activity scores improved versus baseline, and 90% of the patients qualified for treatment prolongation without major differences between nursing level groups. The proportion of patients able to self-inject golimumab was 88, 90, and 73% in the intense, medium, and low support groups, respectively. Satisfaction was high in all three nursing support groups. CONCLUSIONS: This prospective open-label study has confirmed the short-term effectiveness of golimumab in three rheumatological diseases, with most of the patients qualifying for reimbursement renewal. The limited sample size and the fact that the vast majority of patients benefited from an intense nursing support did not allow drawing definite conclusions concerning the impact of the nursing level on the treatment effectiveness and changes in the disease activity. Nurses seem however to play a crucial role in this short-term study but this remains to be confirmed in a longer-term study.

Priming reveals differential coding of symbolic and non-symbolic quantities.

Number processing is characterized by the distance and the size effect, but symbolic numbers exhibit smaller effects than non-symbolic numerosities. The difference between symbolic and non-symbolic processing can either be explained by a different kind of underlying representation or by parametric differences within the same type of underlying representation. We performed a primed naming study to investigate this issue. Prime and target format were manipulated (digits or collections of dots) as well as the numerical distance between prime and target value. Qualitatively different priming patterns were observed for the two formats, showing that the underlying representations differed in kind: Digits activated mental number representations of the place coding type, while collections of dots activated number representations of the summation coding type.

Distinct binding properties of the AT(1) receptor antagonist [(3)H]candesartan to intact cells and membrane preparations.

[(3)H]-2-Ethoxy-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1H-benzimidazoline-7-carboxylic acid ([(3)H]candesartan), a non-peptide angiotensin II type 1 receptor (AT(1) receptor) antagonist bound with high affinity and specificity to intact adherent human AT(1) receptor transfected Chinese hamster ovary cells. The binding characteristics were preserved when cells were suspended, but the dissociation was 3-4-fold faster and the affinity 2-fold lower, while examining [(3)H]candesartan binding to cell membranes. These data suggested the role of the intracellular organisation of living CHO-hAT(1) cells in antagonist-AT(1) receptor interactions. Yet, a specific role of microtubule or actin filaments of the cytoskeleton, receptor phosphorylation by Protein Kinase C, membrane polarity, cytoplasmic components like ATP and the need of an intact cell membrane could be excluded. The potential effect of protease degradation or receptor oxidation during the membrane preparation was also unlikely. The dissociation rate and the equilibrium dissociation constant of [(3)H]candesartan increased with the temperature for both intact cells and membranes. Thermodynamic studies suggested that the bonds between candesartan and the hAT(1) receptor may be of different nature in intact CHO-hAT(1) cells and membranes thereof. Whereas the binding was almost completely enthalpy-driven on intact cells, there was a mixed contribution of both enthalpy and entropy on membranes.

Reward modulates adaptations to conflict.

Both cognitive conflict (e.g. Verguts & Notebaert, 2009) and reward signals (e.g. Waszak & Pholulamdeth, 2009) have been proposed to enhance task-relevant associations. Bringing these two notions together, we predicted that reward modulates conflict-based sequential adaptations in cognitive control. This was tested combining either a single flanker task (Experiment 1) or a task-switch paradigm (Experiment 2) with performance-related rewards. Both experiments confirmed that adaptations after conflict were modulated by reward. In the flanker task, this resulted in increased conflict adaptation after rewarded trials. In the task-switching experiment, reward increased the conflict-modulated switch cost. Interestingly, both adaptations to conflict disappeared after no-reward trials. Moreover, individual differences in participants' sensitivity to reward predicted these reward modulations of trial-to-trial adaptations. These findings shed new light on the exact role of cognitive conflict in shaping subsequent behavior.

The neural basis of implicit perceptual sequence learning.

The present fMRI study investigated the neural areas involved in implicit perceptual sequence learning. To obtain more insight in the functional contributions of the brain areas, we tracked both the behavioral and neural time course of the learning process, using a perceptual serial color matching task. Next, to investigate whether the neural time course was specific for perceptual information, imaging results were compared to the results of implicit motor sequence learning, previously investigated using an identical serial color matching task (Gheysen et al., 2010). Results indicated that implicit sequences can be acquired by at least two neural systems: the caudate nucleus and the hippocampus, having different operating principles. The caudate nucleus contributed to the implicit sequence learning process for perceptual as well as motor information in a similar and gradual way. The hippocampus, on the other hand, was engaged in a much faster learning process which was more pronounced for the motor compared to the perceptual task. Interestingly, the perceptual and motor learning process occurred on a comparable implicit level, suggesting that consciousness is not the main determinant factor dissociating the hippocampal from the caudate learning system. This study is not only the first to successfully and unambiguously compare brain activation between perceptual and motor levels of implicit sequence learning, it also provides new insights into the specific hippocampal and caudate learning function.

Influence of the COMT genotype on working memory and brain activity changes during development.

BACKGROUND: The Valine158Methionine (Val158Met) polymorphism of the COMT gene leads to lower enzymatic activity and higher dopamine availability in Met carriers. The Met allele is associated with better performance and reduced prefrontal cortex activation during working memory (WM) tasks in adults. Dopaminergic system changes during adolescence may lead to a reduction of basal dopamine levels, potentially affecting Met allele benefits during development. METHODS: We investigated the association of COMT genotype with behavioral (n = 322) and magnetic resonance imaging data (n = 81-84) collected during performance of a visuospatial WM task and potential changes in these effects during development (reflected in age × genotype interactions). Data were collected from a cross-sectional and longitudinal typically developing sample of 6- to 20-year-olds. RESULTS: Visuospatial WM capacity exhibited an age × genotype interaction, with a benefit of the Met allele emerging after 10 years of age. There was a parallel age × genotype interaction on WM-related activation in the right inferior frontal gyrus and intraparietal sulcus (IPS), with increases in activation with age in the Val/Val group only. Main effects of COMT genotype were also observed in the IPS, with greater gray matter volumes bilaterally and greater right IPS activation in the Val/Val group compared with the Met carriers. CONCLUSIONS: These results suggest that COMT genotype effects on WM brain activity and behavior are not static during development. The full developmental picture should be considered when trying to understand the impact of genetic polymorphisms on the mature cognition of healthy adult or psychiatric populations.