Nonsymbolic Numerosity Maps at the Occipitotemporal Cortex Respond to Symbolic Numbers.

Numerosity, the set size of a group of items, helps guide human and animals' behavior and decisions. Numerosity perception is thought to be a precursor of symbolic numerical cognition. Previously, we uncovered neural populations selectively tuned to numerosities organized in a network of topographic maps in human association cortex. Here we investigate whether these numerosity maps are also involved in the processing of symbolic numbers, using 7T fMRI and a number-detection task. We recruited 7 participants (3 females) and found that the numerosity map at the temporal-occipital cortex (NTO) also responds to symbolic numbers. Furthermore, we found that numerosity-tuned neuronal populations at the NTO map in the left hemisphere are tuned to symbolic numbers. These results reveal different functions of the numerosity maps and support a link between numerosity representation and symbolic number processing in the ventral temporal-occipital cortex.SIGNIFICANCE STATEMENT Humans and other animals share an intuitive "number sense" to approximately represent numerosity. However, humans possess a unique ability to process number symbols (e.g., Arabic numbers). It has been argued that the human understanding of symbolic numbers is rooted in our ability to numerosity perception. Here we investigate whether numerosity-tuned neuronal populations organized at a network of topographic maps also respond to symbolic numbers. We find one of the maps at the temporal-occipital cortex is involved in symbolic numerical cognition and the neuronal populations are tuned to numbers. These results provide evidence for a link between nonsymbolic numerosity and symbolic number processing.

Assessing the ecological validity of numerosity-selective neuronal populations with real-world natural scenes.

Animals and humans are able to quickly and effortlessly estimate the number of items in a set: their numerosity. Numerosity perception is thought to be critical to behavior, from feeding to escaping predators to human mathematical cognition. Virtually, all scientific studies on numerosity mechanisms use well controlled but artificial stimuli to isolate the numerosity dimension from other physical quantities. Here, we probed the ecological validity of these artificial stimuli and evaluate whether an important component in numerosity processing, the numerosity-selective neural populations, also respond to numerosity of items in real-world natural scenes. Using 7T MRI and natural images from a wide range of categories, we provide evidence that the numerosity-tuned neuronal populations show numerosity-selective responses when viewing images from a real-world natural scene. Our findings strengthen the role of numerosity-selective neurons in numerosity perception and provide an important link to their function in numerosity perception in real-world settings.

Attention drives human numerosity-selective responses.

Numerosity, the set size of a group of items, helps guide behavior and decisions. Previous studies have shown that neural populations respond selectively to numerosities. How numerosity is extracted from the visual scene is a longstanding debate, often contrasting low-level visual with high-level cognitive processes. Here, we investigate how attention influences numerosity-selective responses. The stimuli consisted of black and white dots within the same display. Participants' attention was focused on either black or white dots, while we systematically changed the numerosity of black, white, and total dots. Using 7 T fMRI, we show that the numerosity-tuned neural populations respond only when attention is focused on their preferred numerosity, irrespective of the unattended or total numerosities. Without attention, responses to preferred numerosity are suppressed. Unlike traditional effects of attention in the visual cortex, where attention enhances already existing responses, these results suggest that attention is required to drive numerosity-selective responses.

Comparing BOLD and VASO-CBV population receptive field estimates in human visual cortex.

Vascular Space Occupancy (VASO) is an alternative fMRI approach based on changes in Cerebral Blood Volume (CBV). VASO-CBV fMRI can provide higher spatial specificity than the blood oxygenation level-dependent (BOLD) method because the CBV response is thought to be limited to smaller vessels. To investigate how this technique compares to BOLD fMRI for cognitive neuroscience applications, we compared population receptive field (pRF) mapping estimates between BOLD and VASO-CBV. We hypothesized that VASO-CBV would elicit distinct pRF properties compared to BOLD. Specifically, since pRF size estimates also depend on vascular sources, we hypothesized that reduced vascular blurring might yield narrower pRFs for VASO-CBV measurements. We used a VASO sequence with a double readout 3D EPI sequence at 7T to simultaneously measure VASO-CBV and BOLD responses in the visual cortex while participants viewed conventional pRF mapping stimuli. Both VASO-CBV and BOLD images show similar eccentricity and polar angle maps across all participants. Compared to BOLD-based measurements, VASO-CBV yielded lower tSNR and variance explained. The pRF size changed with eccentricity similarly for VASO-CBV and BOLD, and the pRF size estimates were similar for VASO-CBV and BOLD, even when we equate variance explained between VASO-CBV and BOLD. This result suggests that the vascular component of the pRF size is not dominating in either VASO-CBV or BOLD.

The role of neural tuning in quantity perception.

Perception of quantities, such as numerosity, timing, and size, is essential for behavior and cognition. Accumulating evidence demonstrates neurons processing quantities are tuned, that is, have a preferred quantity amount, not only for numerosity, but also other quantity dimensions and sensory modalities. We argue that quantity-tuned neurons are fundamental to understanding quantity perception. We illustrate how the properties of quantity-tuned neurons can underlie a range of perceptual phenomena. Furthermore, quantity-tuned neurons are organized in distinct but overlapping topographic maps. We suggest that this overlap in tuning provides the neural basis for perceptual interactions between different quantities, without the need for a common neural representational code.

Topographic numerosity maps cover subitizing and estimation ranges.

Numerosity, the set size of a group of items, helps guide behaviour and decisions. Non-symbolic numerosities are represented by the approximate number system. However, distinct behavioural performance suggests that small numerosities, i.e. subitizing range, are implemented differently in the brain than larger numerosities. Prior work has shown that neural populations selectively responding (i.e. hemodynamic responses) to small numerosities are organized into a network of topographical maps. Here, we investigate how neural populations respond to large numerosities, well into the ANS. Using 7 T fMRI and biologically-inspired analyses, we found a network of neural populations tuned to both small and large numerosities organized within the same topographic maps. These results demonstrate a continuum of numerosity preferences that progressively cover both the subitizing range and beyond within the same numerosity map, suggesting a single neural mechanism. We hypothesize that differences in map properties, such as cortical magnification and tuning width, underlie known differences in behaviour.

Individualized cognitive neuroscience needs 7T: Comparing numerosity maps at 3T and 7T MRI.

The field of cognitive neuroscience is weighing evidence about whether to move from the current standard field strength of 3 Tesla (3T) to ultra-high field (UHF) of 7T and above. The present study contributes to the evidence by comparing a computational cognitive neuroscience paradigm at 3T and 7T. The goal was to evaluate the practical effects, i.e. model predictive power, of field strength on a numerosity task using accessible pre-processing and analysis tools. Previously, using 7T functional magnetic resonance imaging and biologically-inspired analyses, i.e. population receptive field modelling, we discovered topographical organization of numerosity-selective neural populations in human parietal cortex. Here we show that these topographic maps are also detectable at 3T. However, averaging of many more functional runs was required at 3T to reliably reconstruct numerosity maps. On average, one 7T run had about four times the model predictive power of one 3T run. We believe that this amount of scanning would have made the initial discovery of the numerosity maps on 3T highly infeasible in practice. Therefore, we suggest that the higher signal-to-noise ratio and signal sensitivity of UHF MRI is necessary to build mechanistic models of the organization and function of our cognitive abilities in individual participants.

Tuned neural responses to haptic numerosity in the putamen.

The ability to perceive the numerosity of items in the environment is critical for behavior of species across the evolutionary tree. Though the focus of studies of numerosity perception lays on the parietal and frontal cortices, the ability to perceive numerosity by a range of species suggests that subcortical nuclei may be implicated in the process. Recently, we have uncovered tuned neural responses to haptic numerosity in the human cortex. Here, we questioned whether subcortical nuclei are also engaged in perception of haptic numerosity. To that end, we utilized a task of haptic numerosity exploration, together with population receptive field model of numerosity selective responses measured at ultra-high field MRI (7T). We found tuned neural responses to haptic numerosity in the bilateral putamen. Similar to the cortex, the population receptive fields tuning width increased with numerosity. The tuned responses to numerosity in the putamen extend its role in cognition and propose that the motor-sensory loops of the putamen and basal ganglia might take an active part in numerosity perception and preparation for future action.

Topographic maps and neural tuning for sensory substitution dimensions learned in adulthood in a congenital blind subject.

Topographic maps, a key principle of brain organization, emerge during development. It remains unclear, however, whether topographic maps can represent a new sensory experience learned in adulthood. MaMe, a congenitally blind individual, has been extensively trained in adulthood for perception of a 2D auditory-space (soundscape) where the y- and x-axes are represented by pitch and time, respectively. Using population receptive field mapping we found neural populations tuned topographically to pitch, not only in the auditory cortices but also in the parietal and occipito-temporal cortices. Topographic neural tuning to time was revealed in the parietal and occipito-temporal cortices. Some of these maps were found to represent both axes concurrently, enabling MaMe to represent unique locations in the soundscape space. This case study provides proof of concept for the existence of topographic maps tuned to the newly learned soundscape dimensions. These results suggest that topographic maps can be adapted or recycled in adulthood to represent novel sensory experiences.

Adaptation to visual numerosity changes neural numerosity selectivity.

Perceiving numerosity, i.e. the set size of a group of items, is an evolutionarily preserved ability found in humans and animals. A useful method to infer the neural underpinnings of a given perceptual property is sensory adaptation. Like other primary perceptual attributes, numerosity is susceptible to adaptation. Recently, we have shown numerosity-selective neural populations with a topographic organization in the human brain. Here, we investigated whether numerosity adaptation can affect the numerosity selectivity of these populations using ultra-high field (7 Tesla) functional magnetic resonance imaging (fMRI). Participants viewed stimuli of changing numerosity (1 to 7 dots), which allowed the mapping of numerosity selectivity. We interleaved a low or high numerosity adapter stimulus with these mapping stimuli, repeatedly presenting 1 or 20 dots respectively to adapt the numerosity-selective neural populations. We analyzed the responses using custom-build population receptive field neural models of numerosity encoding and compared estimated numerosity preferences between adaptation conditions. We replicated our previous studies where we found several topographic maps of numerosity-selective responses. We found that overall, numerosity adaptation altered the preferred numerosities within the numerosity maps, resulting in predominantly attractive biases towards the numerosity of the adapter. The differential biases could be explained by the difference between the unadapted preferred numerosity and the numerosity of the adapter, with attractive biases being observed with higher difference. The results could link perceptual numerosity adaptation effects to changes in neural numerosity selectivity.

Topographic maps representing haptic numerosity reveals distinct sensory representations in supramodal networks.

Dedicated maps for cognitive quantities such as timing, size and numerosity support the view that topography is a general principle of brain organization. To date, however, all of these maps were driven by the visual system. Here, we ask whether there are supramodal topographic maps representing cognitive dimensions irrespective of the stimulated sensory modality. We measured haptically and visually driven numerosity-selective neural responses using model-based analyses and ultra-high field (7T) fMRI. We found topographically organized neural populations tuned to haptic numerosity. The responses to visual or haptic numerosity shared a similar cortical network. However, the maps of the two modalities only partially overlap. Thus, although both visual and haptic numerosities are processed in a similar supramodal functional network, the underlying neural populations may be related, but distinct. Therefore, we hypothesize that overlap between modality-specific maps facilitates cross-modal interactions and supramodal representation of cognitive quantities.

A Whole-Body Sensory-Motor Gradient is Revealed in the Medial Wall of the Parietal Lobe.

In 1954, Penfield and Jasper's findings based on electric stimulation of epileptic patients led them to hypothesize that a sensory representation of the body should be found in the precuneus. They termed this representation the "supplementary sensory" area and emphasized that the exact form of this homunculus could not be specified on the basis of their results. In the decades that followed, their prediction was neglected. The precuneus was found to be involved in numerous motor, cognitive and visual processes, but no work was done on its somatotopic organization. Here, we used a periodic experimental design in which 16 human subjects (eight women) moved 20 body parts to investigate the possible body part topography of the precuneus. We found an anterior-to-posterior, dorsal-to-ventral, toes-to-tongue gradient in a mirror orientation to the SMA. When inspecting body-part-specific functional connectivity, we found differential connectivity patterns for the different body parts to the primary and secondary motor areas and parietal and visual areas, and a shared connectivity to the extrastriate body area, another topographically organized area. We suggest that a whole-body gradient can be found in the precuneus and is connected to multiple brain areas with different connectivity for different body parts. Its exact role and relations to the other known functions of the precuneus such as self-processing, motor imagery, reaching, visuomotor and other body-mind functions should be investigated.SIGNIFICANCE STATEMENT Using fMRI, as well as sensitive spectral analysis, we found a new homunculus in the precuneus: an anterior-to-posterior, dorsal-to-ventral, toes-to-tongue somatotopic gradient in a mirror orientation to the SMA. When inspecting body-part-specific functional connectivity, we found differential connectivity patterns for the different body parts to the primary and secondary motor areas, parietal and visual areas, and a shared connectivity to the extrastriate body area, another topographically organized area. We suggest that a whole-body gradient can be found in the precuneus and is connected to multiple brain areas in a body-part-specific manner.

The development of white matter structural changes during the process of deterioration of the visual field.

Emerging evidence suggests that white matter plasticity in the adult brain is preserved after sensory and behavioral modifications. However, little is known about the progression of structural changes during the process of decline in visual input. Here we studied two groups of patients suffering from advanced retinitis pigmentosa with specific deterioration of the visual field: patients who had lost their peripheral visual field, retaining only central ("tunnel") vision, and blind patients with complete visual field loss. Testing of these homogeneous groups made it possible to assess the extent to which the white matter is affected by loss of partial visual input and whether partially preserved visual input suffices to sustain stability in tracts beyond the primary visual system. Our results showed gradual changes in diffusivity that are indicative of degenerative processes in the primary visual pathway comprising the optic tract and the optic radiation. Interestingly, changes were also found in tracts of the ventral stream and the corticospinal fasciculus, depicting a gradual reorganisation of these tracts consequentially to the gradual loss of visual field coverage (from intact perception to partial vision to complete blindness). This reorganisation may point to microstructural plasticity underlying adaptive behavior and cross-modal integration after partial visual deprivation.

The rapid development of structural plasticity through short water maze training: A DTI study.

Diffusion MRI is sensitive to the microstructure of tissue and allows the study of structural plasticity over short time scales of only hours. The initial temporal and spatial progression of this process, however, has yet to be elucidated. With the aim of examining early temporal progression of structural plasticity, we subjected rats to short training periods on a task in the Morris water maze (MWM), a paradigm previously shown to induce rapid changes in diffusion tensor imaging (DTI) indices. Two groups of rats were each divided into subgroups that consecutively completed 1, 2 or 3 sets of short trials (up to 60s) in the MWM. Each set comprised 4 trials (1 from each quadrant of the WMW), with a specific time interval between sets. To assess the effect of the duration of the task on the evolving changes in DTI indices, we allowed a rest of 45min between sets in one group of rats and a 2-h rest in the other. All rats were scanned with a DTI protocol before and 45min after their last trial. We found that a few minutes of training in a new task sufficed to generate changes in diffusion indices. The earliest changes in DTI (measured after one set of trials) progressed with further training (measured after two sets), but within a few more minutes (after three sets) they reached a plateau. Lengthening the duration of the overall task by prolonging the time interval between sessions did not alter this pattern of change, suggesting that at least within this short time scale such changes are task-dependent, but not time dependent. Our results demonstrate the progression of structural neuroplasticity at different stages of exposure to a novel experience, and show that DTI can be used to trace, in vivo, the localization of structural plasticity induced by training.

Task Selectivity as a Comprehensive Principle for Brain Organization.

How do the anatomically consistent functional selectivities of the brain emerge? A new study by Bola and colleagues reveals task selectivity in auditory rhythm-selective areas in congenitally deaf adults perceiving visual rhythm sequences. Here, we contextualize this result with accumulating evidence from animal and human studies supporting sensory-independent task specializations as a comprehensive principle shaping brain (re)organization.

Rapid language-related plasticity: microstructural changes in the cortex after a short session of new word learning.

Human brain imaging revealed that the brain can undergo structural plasticity following new learning experiences. Most magnetic resonance imaging (MRI) uncovered morphometric alternation in cortical density after the long-term training of weeks to months. A recent diffusion tensor imaging (DTI) study has found changes in diffusion indices after 2 h of training, primarily in the hippocampus. However, whether a short learning experience can induce microstructural changes in the neocortex is still unclear. Here, we used diffusion MRI, a method sensitive to tissue microstructure, to study cortical plasticity. To attain cortical involvement, we used a short language task (under 1 h) of introducing new lexical items (flower names) to the lexicon. We have found significant changes in diffusivity in cortical regions involved in language and reading (inferior frontal gyrus, middle temporal gyrus, and inferior parietal lobule). In addition, the difference in the values of diffusivity correlated with the lexical learning rate in the task. Moreover, significant changes were found in white matter tracts near the cortex, and the extent of change correlated with behavioral measures of lexical learning rate. These findings provide first evidence of short-term cortical plasticity in the human brain after a short language learning task. It seems that short training of less than an hour of high cognitive demand can induce microstructural changes in the cortex, suggesting a rapid time scale of neuroplasticity and providing additional evidence of the power of MRI to investigate the temporal and spatial progressions of this process.

Short-term learning induces white matter plasticity in the fornix.

Magnetic resonance imaging (MRI) has greatly extended the exploration of neuroplasticity in behaving animals and humans. Imaging studies recently uncovered structural changes that occur in gray and white matter, mainly after long-term training. A recent diffusion tensor imaging (DTI) study showed that training in a car racing game for 2 h induces changes in the hippocampus and parahippocampal gyri. However, the effect of short-term training on the white matter microstructure is unknown. Here we investigated the influence of short learning tasks on structural plasticity in the white matter, and specifically in the fornix, in humans and rats. Human subjects performed a 2 h spatial learning task, and rats underwent training for 1 d in a Morris water maze. Between tasks, subjects were scanned with DTI, a diffusion MRI framework sensitive to tissue microstructure. Using tract-based spatial statistics, we found changes in diffusivity indices in both humans and rats. In both species, changes in diffusion in the fornix were correlated with diffusion changes in the hippocampus, as well as with behavioral measures of improvement in the learning tasks. These results, which provide the first indication of short-term white matter plasticity in the human brain, suggest that the adult brain white matter preserves dynamic characteristics and can be modified by short-term learning experiences. The extent of change in white matter was correlated with their extent in gray matter, suggesting that all components of the neural network are capable of rapid remodeling in response to cognitive experiences.

The CONNECT project: Combining macro- and micro-structure.

In recent years, diffusion MRI has become an extremely important tool for studying the morphology of living brain tissue, as it provides unique insights into both its macrostructure and microstructure. Recent applications of diffusion MRI aimed to characterize the structural connectome using tractography to infer connectivity between brain regions. In parallel to the development of tractography, additional diffusion MRI based frameworks (CHARMED, AxCaliber, ActiveAx) were developed enabling the extraction of a multitude of micro-structural parameters (axon diameter distribution, mean axonal diameter and axonal density). This unique insight into both tissue microstructure and connectivity has enormous potential value in understanding the structure and organization of the brain as well as providing unique insights to abnormalities that underpin disease states. The CONNECT (Consortium Of Neuroimagers for the Non-invasive Exploration of brain Connectivity and Tracts) project aimed to combine tractography and micro-structural measures of the living human brain in order to obtain a better estimate of the connectome, while also striving to extend validation of these measurements. This paper summarizes the project and describes the perspective of using micro-structural measures to study the connectome.

Micro-structural assessment of short term plasticity dynamics.

Diffusion MRI enables the non-invasive investigation of neuroplasticity in the human brain. A recent DTI study has shown that a short learning task of only 2 h can yield changes in diffusion parameters. In the current study we aimed to discover whether a biophysical model of diffusion MRI, the CHARMED framework, which models hindered and restricted compartments within the tissue can constitute a more specific method than DTI to study structural plasticity. In addition we set to explore the time scale of the MRI learning-induced-changes. Subjects were scanned with both DTI and CHARMED before and after participating in the same car-racing task. Repetition of a shorter version of the task was done the following week. Results provide additional support to the former discovery of reduction in mean diffusivity after 2 h training using DTI. In addition we show that the CHARMED framework provides a more sensitive method than DTI for discovering microstructural modification. An increase in the fraction of the restricted compartment (Fr) was found after participating in the tasks. Between tasks values of Fr returned to baseline, reflecting the dynamics of structural remodeling. By modeling different compartments in the tissue we suggest that interpretation of the biological processes that induced changes in diffusion is more straightforward, and allows improved detection of the progression of these changes.