Grabbing subitizing with both hands: bimanual number processing

Visual judgment of small numerosities (<4) is generally assumed to be done through subitizing, which is a faster process than counting. Subitizing has also been shown to occur in haptic judgment of the number of spheres in the hand. Furthermore, interactions have been shown to exist between visually perceived numbers and hand motor action. In this study, we compare enumeration of a set of spheres presented to one hand (unimanual) and enumeration of the same total number of spheres presented divided over the two hands (bimanual). Our results show that, like in vision, a combination of subitizing and counting is used to process numbers in active touch. This shows that numbers are processed in a modality-independent way. This suggests that there are not only interactions between perception of numbers and hand motor action, but rather that number representation is modality-independent

Ghrelińs Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction

Understanding the intricate pathways that modulate appetite and subsequent food intake is of particular importance considering the rise in the incidence of obesity across the globe. The serotonergic system, specifically the 5-HT2C receptor, has been shown to be of critical importance in the regulation of appetite and satiety. The GHS-R1a receptor is another key receptor that is well-known for its role in the homeostatic control of food intake and energy balance. We recently showed compelling evidence for an interaction between the GHS-R1a receptor and the 5-HT2C receptor in an in vitro cell line system heterologously expressing both receptors. Here, we investigated this interaction further. First, we show that the GHS-R1a/5-HT2C dimer-induced attenuation of calcium signaling is not due to coupling to GαS, as no increase in cAMP signaling is observed. Next, flow cytometry fluorescence resonance energy transfer (fcFRET) is used to further demonstrate the direct interaction between the GHS-R1a receptor and 5-HT2C receptor. In addition, we demonstrate colocalized expression of the 5-HT2C and GHS-R1a receptor in cultured primary hypothalamic and hippocampal rat neurons, supporting the biological relevance of a physiological interaction. Furthermore, we demonstrate that when 5-HT2C receptor signaling is blocked ghreliņs orexigenic effect is potentiated in vivo. In contrast, the specific 5-HT2C receptor agonist lorcaserin, recently approved for the treatment of obesity, attenuates ghrelin-induced food intake. This underscores the biological significance of our in vitro findings of 5-HT2C receptor-mediated attenuation of GHS-R1a receptor activity. Together, this study demonstrates, for the first time, that the GHS-R1a/5-HT2C receptor interaction translates into a biologically significant modulation of ghreliņs orexigenic effect. This data highlights the potential development of a combined GHS-R1a and 5-HT2C receptor treatment strategy in weight management.Instituto Multidisciplinario de Biología Celula

Differential gene expression in the mesocorticolimbic system of innately high- and low-impulsive rats

Impulsivity is an important component of many psychiatric illnesses and has been associated with a number of psychiatric disorders such as bipolar disorder and attention deficit / hyperactivity disorder (ADHD). Exploring the different aspects of impulsive behaviour and assigning these to specific neurobiological pathways would advance our interpretation of disorders for which impulsivity is key. Pharmacological studies have implicated a number of neurotransmitters in impulsivity, which in turn have been shown to be affected by several genes in both rodent and human studies of impulsivity. Here, we examine impulsivity-related differences in gene expression in finer detail, using the 2-choice serial reaction time task (2-CSRTT) to assess the molecular signature of impulsivity in brain regions previously linked to impulsive behaviour. Wistar rats were rated as high, (n = 6), intermediate, (n = 12) or low impulsive (n = 6), based on premature responses in the 2-CSRTT, after which RNA was extracted from the nucleus accumbens core (NAcc) and ventral prefrontal cortex (vPFC). RNA from the NAcc and vPFC of high and low impulsivity rats (n = 6 per group) was analysed for differential gene expression patterns and exon usage using RNA poly-A tail sequencing. Pnisr, Mal, and Tspan2 were significantly increased in the NAcc of highly impulsive rats, whereas Ube3a was significantly decreased. No differences were seen in the vPFC. In addition to changes in gene expression, Tspan2 displayed differential exon usage in impulsive rats, while functionally, gene expression changes were related to membrane depolarisation and changes in exon usage were linked to sphingolipid breakdown. The changes in gene expression and exon usage observed in this study represent an important step towards defining the molecular architecture of impulsivity. This study therefore represents an important starting point for analysis of the biological role of impulsivity in addiction and other neurological conditions associated with impulsive phenotypes

The effect of feature saliency on haptic subitizing

‘Subitizing’ refers to fast and error-free numerosity judgment for small (<4) sets of items. For larger sets, the slower process of ‘counting’ is used. Counting has a serial character, whereas subitizing is believed to have a parallel character. While subitizing was initially found in vision, it has been shown to exist in touch as well. In vision, it has been demonstrated that adding distractor items to a set of target items influences numerosity judgment of the target items. Subitizing was in this case only possible if the distractor item is highly salient among the targets. In the present study, we investigated the effect of adding a distractor item on haptic judgement of a set of target items. To this end, we asked subjects to judge the number of spheres grasped in their hand. Either a cube or an ellipsoid could be added to the set. A cube among spheres has been shown to be highly salient, while an ellipsoid among spheres is not. Our results show that adding a distractor item led to an increase in the response time slopes regardless of the distractor shape. Subitizing was, however, only possible in the case of a salient distractor. This is in agreement with results from vision

Range dependent processing of visual numerosity: similarities across vision and haptics

‘Subitizing’ refers to fast and accurate judgement of small numerosities, whereas for larger numerosities either counting or estimation are used. Counting is slow and precise, whereas estimation is fast but imprecise. In this study consisting of five experiments we investigated if and how the numerosity judgement process is affected by the relative spacing between the presented numerosities. To this end we let subjects judge the number of dots presented on a screen and recorded their response times. Our results show that subjects switch from counting to estimation if the relative differences between subsequent numerosities are large (a factor of 2), but that numerosity judgement in the subitizing range was still faster. We also show this fast performance for small numerosities only occurred when numerosity information is present. This indicates this is typical for number processing and not magnitude estimation in general. Furthermore, comparison with a previous haptic study suggests similar processing in numerosity judgement through haptics and vision

Inferring Binding Energies from Selected Binding Sites

We employ a biophysical model that accounts for the non-linear relationship between binding energy and the statistics of selected binding sites. The model includes the chemical potential of the transcription factor, non-specific binding affinity of the protein for DNA, as well as sequence-specific parameters that may include non-independent contributions of bases to the interaction. We obtain maximum likelihood estimates for all of the parameters and compare the results to standard probabilistic methods of parameter estimation. On simulated data, where the true energy model is known and samples are generated with a variety of parameter values, we show that our method returns much more accurate estimates of the true parameters and much better predictions of the selected binding site distributions. We also introduce a new high-throughput SELEX (HT-SELEX) procedure to determine the binding specificity of a transcription factor in which the initial randomized library and the selected sites are sequenced with next generation methods that return hundreds of thousands of sites. We show that after a single round of selection our method can estimate binding parameters that give very good fits to the selected site distributions, much better than standard motif identification algorithms

Processing Ordinality and Quantity: The Case of Developmental Dyscalculia

In contrast to quantity processing, up to date, the nature of ordinality has received little attention from researchers despite the fact that both quantity and ordinality are embodied in numerical information. Here we ask if there are two separate core systems that lie at the foundations of numerical cognition: (1) the traditionally and well accepted numerical magnitude system but also (2) core system for representing ordinal information. We report two novel experiments of ordinal processing that explored the relation between ordinal and numerical information processing in typically developing adults and adults with developmental dyscalculia (DD). Participants made “ordered” or “non-ordered” judgments about 3 groups of dots (non-symbolic numerical stimuli; in Experiment 1) and 3 numbers (symbolic task: Experiment 2). In contrast to previous findings and arguments about quantity deficit in DD participants, when quantity and ordinality are dissociated (as in the current tasks), DD participants exhibited a normal ratio effect in the non-symbolic ordinal task. They did not show, however, the ordinality effect. Ordinality effect in DD appeared only when area and density were randomized, but only in the descending direction. In the symbolic task, the ordinality effect was modulated by ratio and direction in both groups. These findings suggest that there might be two separate cognitive representations of ordinal and quantity information and that linguistic knowledge may facilitate estimation of ordinal information

Delays without Mistakes: Response Time and Error Distributions in Dual-Task

BACKGROUND: When two tasks are presented within a short interval, a delay in the execution of the second task has been systematically observed. Psychological theorizing has argued that while sensory and motor operations can proceed in parallel, the coordination between these modules establishes a processing bottleneck. This model predicts that the timing but not the characteristics (duration, precision, variability...) of each processing stage are affected by interference. Thus, a critical test to this hypothesis is to explore whether the quality of the decision is unaffected by a concurrent task. METHODOLOGY/PRINCIPAL FINDINGS: In number comparison--as in most decision comparison tasks with a scalar measure of the evidence--the extent to which two stimuli can be discriminated is determined by their ratio, referred as the Weber fraction. We investigated performance in a rapid succession of two non-symbolic comparison tasks (number comparison and tone discrimination) in which error rates in both tasks could be manipulated parametrically from chance to almost perfect. We observed that dual-task interference has a massive effect on RT but does not affect the error rates, or the distribution of errors as a function of the evidence. CONCLUSIONS/SIGNIFICANCE: Our results imply that while the decision process itself is delayed during multiple task execution, its workings are unaffected by task interference, providing strong evidence in favor of a sequential model of task execution