Processing of quantitative information, investigated with fMRI.

Ever since the discovery of the ‘number neurons’, the neural representation of quantity in the brain has been thought of as a number-selective coding system. In such a system, the neuron is activated by a specific quantity but numerically close quantities also activate the neuron. Recent fMRI studies also confirmed the existence of a number-selective system in humans. Several computational modelling studies predicted a number-sensitive coding stage as a necessary preceding stage to the number-selective neurons (Verguts & Fias, 2004). In this coding scheme, the coding is analogous to the number it represents. This can be implemented by neurons that respond monotonically to number (e.g., more strongly for larger numbers). Recently, the biological reality of such a system has been demonstrated by use of single-cell recording, in the lateral intraparietal area (LIP) of the macaque monkey. In this thesis, we searched for evidence of number-sensitive coding in humans. Using a priming paradigm, we found behavioural evidence for a number-sensitive system in humans for small non-symbolic numerosities (1 to 5). Using event-related fMRI, we showed number-sensitive activation in the human LIP area in the same number range. Remarkably, we could not extend these results for larger numerosities (2 to 64). Whereas the lack of results in the behavioural priming experiment could be due to an insensitivity of the method, this was not a plausible explanation in the fMRI experiment, as the activity measured in human LIP significantly decreased for numerosities larger than 8. We therefore concluded that the number-sensitive system is liable to a capacity limit for higher numerosities, which could be caused by the use of lateral inhibition. We further suggest that the implementation of this lateral inhibition is dependent on the particular task set, and that the capacity limit is not present (or less stringent) when numerosity is not behaviourally relevant. This could explain the finding of number-sensitive neurons for larger numerosities in monkeys. Finally, we suggest that a different mechanism is employed when numerical value of large numerosities is relevant. This leads to the conclusion that dot patterns in the small and large number range are processed differently

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

Image Aquisition Order and Input Order of BOLD-fMRI Data for Slice Time Correction in fMRI Data Processing Tools

C

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

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

Priming reveals differential coding of symbolic and non-symbolic quantities

A

Number processing pathways in human parietal cortex

to this work. 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 numberselective 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