rTMS over the intraparietal sulcus disrupts numerosity processing

It has been widely argued that the intraparietal sulcus (IPS) is involved in tasks that evoke representations of numerical magnitude, among other cognitive functions. However, the causal role of this parietal region in processing symbolic and non-symbolic numerosity has not been established. The current study used repetitive Transcranial Magnetic Stimulation (rTMS) to the left and right IPS to investigate the effects of temporary deactivations of these regions on the capacity to represent symbolic (Arabic numbers) and non-symbolic (arrays of dots) numerosities. We found that comparisons of both symbolic and non-symbolic numerosities were impaired after rTMS to the left IPS but enhanced by rTMS to the right IPS. A signature effect of numerical distance was also found: greater impairment (or lesser facilitation) when comparing numerosities of similar magnitude. The reverse pattern of impairment and enhancement was found in a control task that required judging an analogue stimulus property (ellipse orientation) but no numerosity judgements. No rTMS effects for the numerosity tasks were found when stimulating an area adjacent but distinct from the IPS, the left and right angular gyrus. These data suggest that left IPS is critical for processing symbolic and non-symbolic numerosity; this processing may thus depend on common neural mechanisms, which are distinct from mechanisms supporting the processing of analogue stimulus properties. H. Barth and F. Fregni contributed equally to this study.     

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.     

Multiple object individuation during numerical Stroop

To investigate whether semantic information relative to numbers is retained during multiple object individuation, we recorded N2pc—a neural measure of selection/individuation—during a numerical version of the Stroop task. Participants enumerated a varying number of target digits (1 to 4) whose identity was either congruent or incongruent with their numerosity. N2pc amplitudes increased as a function of target numerosity but were little affected by congruency, suggesting that multiple object individuation is a prenumeric stage that does not encode for the number magnitude of the numerosity of the individuated objects.     

What eye fixation patterns tell us about subitizing

Differences between the enumeration of very small (1-3) versus larger (4-6) numerosities were examined by investigating where people fixate when they are enumerating different numbers of items. Overall, fixations were more likely to be located in regions of the array that contained target items when the array contained 4 or more targets than when it contained 3 or fewer, a result that is consistent with previous research indicating that the enumeration of very small sets is less dependent on attentional processing than is the enumeration of larger sets. However, both the pattern of fixations across different distractor conditions and an analysis of the temporal course of fixations in the absence of distractors were inconsistent with a dichotomous distinction between pre-attentive and attentional forms of enumeration. Rather, our results suggest that, irrespective of numerosity, enumeration entails some attentional processing of target items, but attentional processing plays a markedly greater role in the enumeration of 4 or more items than in the enumeration of 3 or fewer.     

The effect of entrainment on the timing of periodic eye movements

We performed an experiment in which eight healthy individuals made periodic eye movements at five pacing interval conditions (500 ms, 750 ms, 1000 ms, 1250 ms, and 1500 ms). Three methods of entrainment were used in the synchronization phase: saccade, continuous pursuit and discontinuous pursuit. The stimulus train was extinguished and in the continuation phase, subjects made saccadic eye movements at the entrained movement frequencies between two static targets. Using the Wing–Kristofferson model, clock and motor variance were extracted from the time series of continuation trials for all three entrainment conditions. Our results revealed a main effect of time interval on total variance clock variance (as predicted by Weber's law) and on motor variance. We also report that the pursuit entrainment conditions resulted in and mean duration and variance to the saccade entrainment. These results suggest that the neural networks recruited to support a periodic motor timing task depend on the method used to establish the temporal reference.     

Using EEG to Explore How rTMS Produces Its Effects on Behavior

A commonly held view is that, when delivered during the performance of a task, repetitive TMS (rTMS) influences behavior by producing transient “virtual lesions” in targeted tissue. However, findings of rTMS-related improvements in performance are difficult to reconcile with this assumption. With regard to the mechanism whereby rTMS influences concurrent task performance, a combined rTMS/EEG study conducted in our lab has revealed a complex set of relations between rTMS, EEG activity, and behavioral performance, with the effects of rTMS on power in the alpha band and on alpha:gamma phase synchrony each predicting its effect on behavior. These findings suggest that rTMS influences performance by biasing endogenous task-related oscillatory dynamics, rather than creating a “virtual lesion”. To further differentiate these two alternatives, in the present study we compared the effects of 10 Hz rTMS on neural activity with the results of an experiment in which rTMS was replaced with 10 Hz luminance flicker. We reasoned that 10 Hz flicker would produce widespread entrainment of neural activity to the flicker frequency, and comparison of these EEG results with those from the rTMS study would shed light on whether the latter also reflected entrainment to an exogenous stimulus. Results revealed pronounced evidence for “entrainment noise” produced by 10 Hz flicker—increased oscillatory power and inter-trial coherence (ITC) at the driving frequency, and increased alpha:gamma phase synchronization—that were nonetheless largely uncorrelated with behavior. This contrasts markedly with 10-Hz rTMS, for which the only evidence for stimulation-induced noise, elevated ITC at 30 Hz, differed qualitatively from the flicker results. Simultaneous recording of the EEG thus offers an important means of directly testing assumptions about how rTMS exerts its effects on behavior.     

Magnetoencephalographic Signatures of Numerosity Discrimination in Fetuses and Neonates

Numerosity discrimination has been demonstrated in newborns, but not in fetuses. Fetal magnetoencephalography allows non-invasive investigation of neural responses in neonates and fetuses. During an oddball paradigm with auditory sequences differing in numerosity, evoked responses were recorded and mismatch responses were quantified as an indicator for auditory discrimination. Thirty pregnant women with healthy fetuses (last trimester) and 30 healthy term neonates participated. Fourteen adults were included as a control group. Based on measurements eligible for analysis, all adults, all neonates, and 74% of fetuses showed numerical mismatch responses. Numerosity discrimination appears to exist in the last trimester of pregnancy.     

Emergence of a 'visual number sense' in hierarchical generative models

Numerosity estimation is phylogenetically ancient and foundational to human mathematical learning, but its computational bases remain controversial. Here we show that visual numerosity emerges as a statistical property of images in 'deep networks' that learn a hierarchical generative model of the sensory input. Emergent numerosity detectors had response profiles resembling those of monkey parietal neurons and supported numerosity estimation with the same behavioral signature shown by humans and animals.     

Effects of lesions to the left lateral prefrontal cortex on task-specific top-down biases and response strategies in blocked-cyclic naming

Anders, Riès, van Maanen and Alario put forward evidence accumulation modelling of object naming times as an alternative to neural network models of lexical retrieval. The authors exemplify their approach using data from the blocked-cyclic naming paradigm, requiring speakers to repeatedly name small sets of related or unrelated objects. The effects observed with this paradigm are understood reasonably well within the tradition of neural network modelling. However, implemented neural network models do not specify interfaces for task-specific top-down influences and response strategies that are likely to play a role in the blocked-cyclic naming paradigm, distinguishing it from continuous, non-cyclic manipulations of the naming context. I argue that the evidence accumulation approach falls short on this account as well, as it does not specify the potential contribution of task-specific top-down processes and strategic facilitation effects to the response time distributions. Future endeavours to model or fit data from blocked-cyclic naming experiments should strive to do so by simultaneously considering data from continuous context manipulations.     

Prior event uncertainty reduction under two different levels of time uncertainty of foreperiod duration in schizophrenia

Schizophrenic and alcoholic Ss judged stimulus durations of 0.50 and 0.55 seconds. Stimulus was 1, 3 or 5 dark dots and was preceded by variable fore-period duration of 1, 3 or 5 seconds. Judgment of stimulus duration was found to be a monotonically increasing function of both foreperiod duration and numerosity of dots. When pitch of sound, which functioned as a warning signal, was correlated with numerosity of dots, the monotonic relation between numerosity of dots and estimation of stimulus duration was eliminated for alcoholics, but not for schizophrenics, only when foreperiod duration was constant from trial to trial. The effect of prior information as to numerosity of dots was negligible for both schizophrenics and alcoholics when foreperiod duration was variable from trial to trial.     

Core knowledge of object,number, and geometry: A comparative and neural approach

Studies on the ontogenetic origins of human knowledge provide evidence for a small set of separable systems of core knowledge dealing with the representation of inanimate and animate objects, number, and geometry. Because core knowledge systems are evolutionarily ancient, they can be investigated from a comparative perspective, making use of various animal models. In this review, I discuss evidence showing precocious abilities in nonhuman species to represent (a) objects that move partly or fully out of view and their basic mechanical properties such as solidity, (b) the cardinal and ordinal/sequential aspects of numerical cognition and rudimentary arithmetic with small numerosities, and (c) the geometrical relationships among extended surfaces in the surrounding layout. Controlled rearing studies suggest that the abilities associated with core knowledge systems of objects, number, and geometry are observed in animals in the absence (or with very reduced) experience, supporting a nativistic foundation of such cognitive mechanisms. Animal models also promise a fresh approach to the issue of the neurobiological and genetic mechanisms underlying the expression of core knowledge systems.     

Neural response dynamics of spiking and local field potential activity depend on CRT monitor refresh rate in the tree shrew primary visual cortex

Entrainment of neural activity to luminance impulses during the refresh of cathode ray tube monitor displays has been observed in the primary visual cortex (V1) of humans and macaque monkeys. This entrainment is of interest because it tends to temporally align and thus synchronize neural responses at the millisecond timescale. Here we show that, in tree shrew V1, both spiking and local field potential activity are also entrained at cathode ray tube refresh rates of 120, 90, and 60 Hz, with weakest but still significant entrainment even at 120 Hz, and strongest entrainment occurring in cortical input layer IV. For both luminance increments ("white" stimuli) and decrements ("black" stimuli), refresh rate had a strong impact on the temporal dynamics of the neural response for subsequent luminance impulses. Whereas there was rapid, strong attenuation of spikes and local field potential to prolonged visual stimuli composed of luminance impulses presented at 120 Hz, attenuation was nearly absent at 60-Hz refresh rate. In addition, neural onset latencies were shortest at 120 Hz and substantially increased, by ～15 ms, at 60 Hz. In terms of neural response amplitude, black responses dominated white responses at all three refresh rates. However, black/white differences were much larger at 60 Hz than at higher refresh rates, suggesting a mechanism that is sensitive to stimulus timing. Taken together, our findings reveal many similarities between V1 of macaque and tree shrew, while underscoring a greater temporal sensitivity of the tree shrew visual system.     

Experimental evidence for a neural origin of Ewing''s sarcoma of bone.

The histogenesis of Ewing's sarcoma remains unknown. Recent studies have suggested a relationship to an unusual form of childhood neural tumor, often termed peripheral neuroepithelioma or primitive neuroectodermal tumor. Five Ewing's sarcoma tumor cell lines were studied for evidence of a neural phenotype. Under normal culture conditions, no morphologic evidence of neural differentiation was detected. Treatment with retinoic acid, an agent known to induce marked neural differentiation in neuroblastoma, had no demonstrable effect. Treatment with either cyclic AMP or TPA, in contrast, induced pronounced morphologic evidence of neural differentiation. Cells developed elongate processes with varicosities by phase-contrast microscopy; filaments, microtubules, and uraniffin-positive dense core granules were present by electron microscopy. Three neural markers (NSE, NFTP, and cholinesterase) were absent or barely detectable in untreated cells, but became abundant after treatment. These results provide convincing evidence for a neural histogenesis of Ewing's sarcoma. They also suggest a close relationship between Ewing's sarcoma and peripheral neural tumors, including the chest wall tumor described by Askin, but only a distant relationship to neuroblastoma.     

Sex differences in the circadian control of hamster wheel-running activity

The circadian pacemaker that underlies the wheel-running activity of hamsters was studied in males and females. Sex differences were found in the mechanism by which the pacemaker entrains to light-dark cycles and in the timing of activity onset. When exposed to a light-dark cycle with a period of 24.75 h (with 1 h of light/cycle), males show a greater ability to maintain entrainment than do females. This difference in the upper limit of entrainment appears due to a sex difference in the magnitude of light-induced phase shifts. A small difference in free-running period may also contribute to the sex difference in entrainment. Two weeks after castration of adults, the sex difference in entrainment is not affected, indicating that the difference does not depend on circulating gonadal steroids or on estrous cyclicity of the female. However, castration of females at an early age increases their ability to entrain, whereas long-term castration of males seems to reduce entrainment ability. During entrainment to a 24-h light-dark cycle (LD 14:10), females were found to begin their daily activity before males and before castrated females. This difference is consistent with a sex difference in the magnitude of light-induced phase shifts and in entrainment of the pacemaker. However, evidence is given that the sex difference in activity onset might also be caused by a sex difference in the relationship of locomotor activity to the pacemaker in intact males and females.     

Who is honest and why: Baseline activation in anterior insula predicts inter-individual differences in deceptive behavior

Humans engage in deceptive behavior that negatively affects others. The propensity to deceive is, however, characterized by vast inter-individual heterogeneity that is poorly understood. Attempts to investigate the origins of this heterogeneity have so far mainly relied on subjective measures and have shown little predictive power. Here, we used resting electroencephalography to measure objective and stable individual differences in neural baseline activation in combination with an ecologically valid deception paradigm. Results showed that task-independent baseline activation in the anterior insula, a brain area implicated in mapping internal bodily states and in representing emotional arousal and conscious feelings, predicts individuals’ propensity for deceptive behavior. The higher the neural baseline activation in this area is, the lower individuals’ propensity to deceive. Moreover, results provide evidence that high baseline activation in the anterior insula is associated with negative affect and dispositional tendencies to avoid aversive emotional situations. These results provide converging neural and psychological evidence that individuals might avoid a deceptive act due to a highly active negative emotional system which would make a deceptive act too stressful and bothersome.     

Neural correlates of evidence accumulation in a perceptual decision task

Sequential sampling models provide a useful framework for understanding human decision making. A key component of these models is an evidence accumulation process in which information is accrued over time to a threshold, at which point a choice is made. Previous neurophysiological studies on perceptual decision making have suggested accumulation occurs only in sensorimotor areas involved in making the action for the choice. Here we investigated the neural correlates of evidence accumulation in the human brain using functional magnetic resonance imaging (fMRI) while manipulating the quality of sensory evidence, the response modality, and the foreknowledge of the response modality. We trained subjects to perform a random dot motion direction discrimination task by either moving their eyes or pressing buttons to make their responses. In addition, they were cued about the response modality either in advance of the stimulus or after a delay. We isolated fMRI responses for perceptual decisions in both independently defined sensorimotor areas and task-defined nonsensorimotor areas. We found neural signatures of evidence accumulation, a higher fMRI response on low coherence trials than high coherence trials, primarily in saccade-related sensorimotor areas (frontal eye field and intraparietal sulcus) and nonsensorimotor areas in anterior insula and inferior frontal sulcus. Critically, such neural signatures did not depend on response modality or foreknowledge. These results help establish human brain areas involved in evidence accumulation and suggest that the neural mechanism for evidence accumulation is not specific to effectors. Instead, the neural system might accumulate evidence for particular stimulus features relevant to a perceptual task.     

A mechanism for value-guided choice based on the excitation-inhibition balance in prefrontal cortex

Although the ventromedial prefrontal cortex (vmPFC) has long been implicated in reward-guided decision making, its exact role in this process has remained an unresolved issue. Here we show that, in accordance with models of decision making, vmPFC concentrations of GABA and glutamate in human volunteers predict both behavioral performance and the dynamics of a neural value comparison signal. These data provide evidence for a neural competition mechanism in vmPFC that supports value-guided choice.     

Daily activity patterns of a nocturnal and a diurnal rodent in a seminatural environment

The entrainment of circadian rhythms by light-dark (LD) cycles has been extensively investigated in laboratory studies. In almost all of these studies, organisms have not been allowed to modulate their exposure to the LD cycle. In the present study, the rhythm of running-wheel activity was investigated in nocturnal (domestic mice) and diurnal (Nile grass rats) rodents provided with light-tight nest boxes and maintained under long and short photoperiods. Photoperiod length had a significant effect on the duration of the daily active phase (alpha), on the phase angle of entrainment (psi), and on diurnality or nocturnality in both species. The availability of a nest box had a modest effect only on the variability of activity onsets. Neither in the nocturnal nor in the diurnal species was there any evidence of entrainment by frequency demultiplication or of entrainment without photic stimulation at either dawn or dusk. These results indicate that at least in the species studied, the ability of rodents to modulate their exposure to the LD cycle does not have a major effect on photic entrainment.     

Attentional processing of multiple targets and distractors

We assessed the functioning of attention when multiple relevant objects are intermingled with multiple distractors, measuring two electrophysiological subcomponents of the N2pc that have been associated, respectively, with target selection and distractor suppression: the target negativity (Nt) and the distractor positivity (Pd). To this aim, we orthogonally manipulated the number of targets and distractors in an enumeration task. The Nt was modulated by target, but not distractor numerosity, suggesting that an increase in target numerosity leads to an increase in attentional resources needed to form individual representations of the targets. In contrast, the number of distractors did not differentially alter the Pd. We hypothesize that distractors sharing similar visual features can be processed (and possibly suppressed) as a set, without the need for individuation.