Principles of intensive human neuroimaging.

The rise of large, publicly shared functional magnetic resonance imaging (fMRI) data sets in human neuroscience has focused on acquiring either a few hours of data on many individuals ('wide' fMRI) or many hours of data on a few individuals ('deep' fMRI). In this opinion article, we highlight an emerging approach within deep fMRI, which we refer to as 'intensive' fMRI: one that strives for extensive sampling of cognitive phenomena to support computational modeling and detailed investigation of brain function at the single voxel level. We discuss the fundamental principles, trade-offs, and practical considerations of intensive fMRI. We also emphasize that intensive fMRI does not simply mean collecting more data: it requires careful design of experiments to enable a rich hypothesis space, optimizing data quality, and strategically curating public resources to maximize community impact.

A large-scale examination of inductive biases shaping high-level visual representation in brains and machines.

The rapid release of high-performing computer vision models offers new potential to study the impact of different inductive biases on the emergent brain alignment of learned representations. Here, we perform controlled comparisons among a curated set of 224 diverse models to test the impact of specific model properties on visual brain predictivity - a process requiring over 1.8 billion regressions and 50.3 thousand representational similarity analyses. We find that models with qualitatively different architectures (e.g. CNNs versus Transformers) and task objectives (e.g. purely visual contrastive learning versus vision- language alignment) achieve near equivalent brain predictivity, when other factors are held constant. Instead, variation across visual training diets yields the largest, most consistent effect on brain predictivity. Many models achieve similarly high brain predictivity, despite clear variation in their underlying representations - suggesting that standard methods used to link models to brains may be too flexible. Broadly, these findings challenge common assumptions about the factors underlying emergent brain alignment, and outline how we can leverage controlled model comparison to probe the common computational principles underlying biological and artificial visual systems.

Engaging in word recognition elicits highly specific modulations in visual cortex.

A person's cognitive state determines how their brain responds to visual stimuli. The most common such effect is a response enhancement when stimuli are task relevant and attended rather than ignored. In this fMRI study, we report a surprising twist on such attention effects in the visual word form area (VWFA), a region that plays a key role in reading. We presented participants with strings of letters and visually similar shapes, which were either relevant for a specific task (lexical decision or gap localization) or ignored (during a fixation dot color task). In the VWFA, the enhancement of responses to attended stimuli occurred only for letter strings, whereas non-letter shapes evoked smaller responses when attended than when ignored. The enhancement of VWFA activity was accompanied by strengthened functional connectivity with higher-level language regions. These task-dependent modulations of response magnitude and functional connectivity were specific to the VWFA and absent in the rest of visual cortex. We suggest that language regions send targeted excitatory feedback into the VWFA only when the observer is trying to read. This feedback enables the discrimination of familiar and nonsense words and is distinct from generic effects of visual attention.

Color-biased regions in the ventral visual pathway are food selective.

Color-biased regions have been found between face- and place-selective areas in the ventral visual pathway. To investigate the function of the color-biased regions in a pathway responsible for object recognition, we analyzed the natural scenes dataset (NSD), a large 7T fMRI dataset from 8 participants who each viewed up to 30,000 trials of images of colored natural scenes over more than 30 scanning sessions. In a whole-brain analysis, we correlated the average color saturation of the images with voxel responses, revealing color-biased regions that diverge into two streams, beginning in V4 and extending medially and laterally relative to the fusiform face area in both hemispheres. We drew regions of interest (ROIs) for the two streams and found that the images for each ROI that evoked the largest responses had certain characteristics: they contained food, circular objects, warmer hues, and had higher color saturation. Further analyses showed that food images were the strongest predictor of activity in these regions, implying the existence of medial and lateral ventral food streams (VFSs). We found that color also contributed independently to voxel responses, suggesting that the medial and lateral VFSs use both color and form to represent food. Our findings illustrate how high-resolution datasets such as the NSD can be used to disentangle the multifaceted contributions of many visual features to the neural representations of natural scenes.

Improving the accuracy of single-trial fMRI response estimates using GLMsingle.

Advances in artificial intelligence have inspired a paradigm shift in human neuroscience, yielding large-scale functional magnetic resonance imaging (fMRI) datasets that provide high-resolution brain responses to thousands of naturalistic visual stimuli. Because such experiments necessarily involve brief stimulus durations and few repetitions of each stimulus, achieving sufficient signal-to-noise ratio can be a major challenge. We address this challenge by introducing GLMsingle, a scalable, user-friendly toolbox available in MATLAB and Python that enables accurate estimation of single-trial fMRI responses (glmsingle.org). Requiring only fMRI time-series data and a design matrix as inputs, GLMsingle integrates three techniques for improving the accuracy of trial-wise general linear model (GLM) beta estimates. First, for each voxel, a custom hemodynamic response function (HRF) is identified from a library of candidate functions. Second, cross-validation is used to derive a set of noise regressors from voxels unrelated to the experiment. Third, to improve the stability of beta estimates for closely spaced trials, betas are regularized on a voxel-wise basis using ridge regression. Applying GLMsingle to the Natural Scenes Dataset and BOLD5000, we find that GLMsingle substantially improves the reliability of beta estimates across visually-responsive cortex in all subjects. Comparable improvements in reliability are also observed in a smaller-scale auditory dataset from the StudyForrest experiment. These improvements translate into tangible benefits for higher-level analyses relevant to systems and cognitive neuroscience. We demonstrate that GLMsingle: (i) helps decorrelate response estimates between trials nearby in time; (ii) enhances representational similarity between subjects within and across datasets; and (iii) boosts one-versus-many decoding of visual stimuli. GLMsingle is a publicly available tool that can significantly improve the quality of past, present, and future neuroimaging datasets sampling brain activity across many experimental conditions.

Variability of the Surface Area of the V1, V2, and V3 Maps in a Large Sample of Human Observers.

How variable is the functionally defined structure of early visual areas in human cortex and how much variability is shared between twins? Here we quantify individual differences in the best understood functionally defined regions of cortex: V1, V2, V3. The Human Connectome Project 7T Retinotopy Dataset includes retinotopic measurements from 181 subjects (109 female, 72 male), including many twins. We trained four "anatomists" to manually define V1-V3 using retinotopic features. These definitions were more accurate than automated anatomical templates and showed that surface areas for these maps varied more than threefold across individuals. This threefold variation was little changed when normalizing visual area size by the surface area of the entire cerebral cortex. In addition to varying in size, we find that visual areas vary in how they sample the visual field. Specifically, the cortical magnification function differed substantially among individuals, with the relative amount of cortex devoted to central vision varying by more than a factor of 2. To complement the variability analysis, we examined the similarity of visual area size and structure across twins. Whereas the twin sample sizes are too small to make precise heritability estimates (50 monozygotic pairs, 34 dizygotic pairs), they nonetheless reveal high correlations, consistent with strong effects of the combination of shared genes and environment on visual area size. Collectively, these results provide the most comprehensive account of individual variability in visual area structure to date, and provide a robust population benchmark against which new individuals and developmental and clinical populations can be compared.SIGNIFICANCE STATEMENT Areas V1, V2, and V3 are among the best studied functionally defined regions in human cortex. Using the largest retinotopy dataset to date, we characterized the variability of these regions across individuals and the similarity between twin pairs. We find that the size of visual areas varies dramatically (up to 3.5×) across healthy young adults, far more than the variability of the cerebral cortex size as a whole. Much of this variability appears to arise from inherited factors, as we find very high correlations in visual area size between monozygotic twin pairs, and lower but still substantial correlations between dizygotic twin pairs. These results provide the most comprehensive assessment of how functionally defined visual cortex varies across the population to date.

The retrocalcarine sulcus maps different retinotopic representations in macaques and humans.

Primate cerebral cortex is highly convoluted with much of the cortical surface buried in sulcal folds. The origins of cortical folding and its functional relevance have been a major focus of systems and cognitive neuroscience, especially when considering stereotyped patterns of cortical folding that are shared across individuals within a primate species and across multiple species. However, foundational questions regarding organizing principles shared across species remain unanswered. Taking a cross-species comparative approach with a careful consideration of historical observations, we investigate cortical folding relative to primary visual cortex (area V1). We identify two macroanatomical structures-the retrocalcarine and external calcarine sulci-in 24 humans and 6 macaque monkeys. We show that within species, these sulci are identifiable in all individuals, fall on a similar part of the V1 retinotopic map, and thus, serve as anatomical landmarks predictive of functional organization. Yet, across species, the underlying eccentricity representations corresponding to these macroanatomical structures differ strikingly across humans and macaques. Thus, the correspondence between retinotopic representation and cortical folding for an evolutionarily old structure like V1 is species-specific and suggests potential differences in developmental and experiential constraints across primates.

Sensory Recruitment Revisited: Ipsilateral V1 Involved in Visual Working Memory.

The "sensory recruitment hypothesis" posits an essential role of sensory cortices in working memory, beyond the well-accepted frontoparietal areas. Yet, this hypothesis has recently been challenged. In the present study, participants performed a delayed orientation recall task while high-spatial-resolution 3 T functional magnetic resonance imaging (fMRI) signals were measured in posterior cortices. A multivariate inverted encoding model approach was used to decode remembered orientations based on blood oxygen level-dependent fMRI signals from visual cortices during the delay period. We found that not only did activity in the contralateral primary visual cortex (V1) retain high-fidelity representations of the visual stimuli, but activity in the ipsilateral V1 also contained such orientation tuning. Moreover, although the encoded tuning was faded in the contralateral V1 during the late delay period, tuning information in the ipsilateral V1 remained sustained. Furthermore, the ipsilateral representation was presented in secondary visual cortex (V2) as well, but not in other higher-level visual areas. These results thus supported the sensory recruitment hypothesis and extended it to the ipsilateral sensory areas, which indicated the distributed involvement of visual areas in visual working memory.

Distinct Representations of Tonotopy and Pitch in Human Auditory Cortex.

Frequency-to-place mapping, or tonotopy, is a fundamental organizing principle throughout the auditory system, from the earliest stages of auditory processing in the cochlea to subcortical and cortical regions. Although cortical maps are referred to as tonotopic, it is unclear whether they simply reflect a mapping of physical frequency inherited from the cochlea, a computation of pitch based on the fundamental frequency, or a mixture of these two features. We used high-resolution functional magnetic resonance imaging (fMRI) to measure BOLD responses as male and female human participants listened to pure tones that varied in frequency or complex tones that varied in either spectral content (brightness) or fundamental frequency (pitch). Our results reveal evidence for pitch tuning in bilateral regions that partially overlap with the traditional tonotopic maps of spectral content. In general, primary regions within Heschl's gyri (HGs) exhibited more tuning to spectral content, whereas areas surrounding HGs exhibited more tuning to pitch.SIGNIFICANCE STATEMENT Tonotopy, an orderly mapping of frequency, is observed throughout the auditory system. However, it is not known whether the tonotopy observed in the cortex simply reflects the frequency spectrum (as in the ear) or instead represents the higher-level feature of fundamental frequency, or pitch. Using carefully controlled stimuli and high-resolution functional magnetic resonance imaging (fMRI), we separated these features to study their cortical representations. Our results suggest that tonotopy in primary cortical regions is driven predominantly by frequency, but also reveal evidence for tuning to pitch in regions that partially overlap with the tonotopic gradients but extend into nonprimary cortical areas. In addition to resolving ambiguities surrounding cortical tonotopy, our findings provide evidence that selectivity for pitch is distributed bilaterally throughout auditory cortex.

Ultra-high-resolution fMRI of Human Ventral Temporal Cortex Reveals Differential Representation of Categories and Domains.

Human ventral temporal cortex (VTC) is critical for visual recognition. It is thought that this ability is supported by large-scale patterns of activity across VTC that contain information about visual categories. However, it is unknown how category representations in VTC are organized at the submillimeter scale and across cortical depths. To fill this gap in knowledge, we measured BOLD responses in medial and lateral VTC to images spanning 10 categories from five domains (written characters, bodies, faces, places, and objects) at an ultra-high spatial resolution of 0.8 mm using 7 Tesla fMRI in both male and female participants. Representations in lateral VTC were organized most strongly at the general level of domains (e.g., places), whereas medial VTC was also organized at the level of specific categories (e.g., corridors and houses within the domain of places). In both lateral and medial VTC, domain-level and category-level structure decreased with cortical depth, and downsampling our data to standard resolution (2.4 mm) did not reverse differences in representations between lateral and medial VTC. The functional diversity of representations across VTC partitions may allow downstream regions to read out information in a flexible manner according to task demands. These results bridge an important gap between electrophysiological recordings in single neurons at the micron scale in nonhuman primates and standard-resolution fMRI in humans by elucidating distributed responses at the submillimeter scale with ultra-high-resolution fMRI in humans.SIGNIFICANCE STATEMENT Visual recognition is a fundamental ability supported by human ventral temporal cortex (VTC). However, the nature of fine-scale, submillimeter distributed representations in VTC is unknown. Using ultra-high-resolution fMRI of human VTC, we found differential distributed visual representations across lateral and medial VTC. Domain representations (e.g., faces, bodies, places, characters) were most salient in lateral VTC, whereas category representations (e.g., corridors/houses within the domain of places) were equally salient in medial VTC. These results bridge an important gap between electrophysiological recordings in single neurons at a micron scale and fMRI measurements at a millimeter scale.

An image-computable model for the stimulus selectivity of gamma oscillations.

Gamma oscillations in visual cortex have been hypothesized to be critical for perception, cognition, and information transfer. However, observations of these oscillations in visual cortex vary widely; some studies report little to no stimulus-induced narrowband gamma oscillations, others report oscillations for only some stimuli, and yet others report large oscillations for most stimuli. To better understand this signal, we developed a model that predicts gamma responses for arbitrary images and validated this model on electrocorticography (ECoG) data from human visual cortex. The model computes variance across the outputs of spatially pooled orientation channels, and accurately predicts gamma amplitude across 86 images. Gamma responses were large for a small subset of stimuli, differing dramatically from fMRI and ECoG broadband (non-oscillatory) responses. We propose that gamma oscillations in visual cortex serve as a biomarker of gain control rather than being a fundamental mechanism for communicating visual information.

GLMdenoise improves multivariate pattern analysis of fMRI data.

GLMdenoise is a denoising technique for task-based fMRI. In GLMdenoise, estimates of spatially correlated noise (which may be physiological, instrumental, motion-related, or neural in origin) are derived from the data and incorporated as nuisance regressors in a general linear model (GLM) analysis. We previously showed that GLMdenoise outperforms a variety of other denoising techniques in terms of cross-validation accuracy of GLM estimates (Kay et al., 2013a). However, the practical impact of denoising for experimental studies remains unclear. Here we examine whether and to what extent GLMdenoise improves sensitivity in the context of multivariate pattern analysis of fMRI data. On a large number of participants (31 participants across 4 experiments; 3 T, gradient-echo, spatial resolution 2-3.75 mm, temporal resolution 1.3-2 s, number of conditions 32-75), we perform representational similarity analysis (Kriegeskorte et al., 2008a) as well as pattern classification (Haxby et al., 2001). We find that GLMdenoise substantially improves replicability of representational dissimilarity matrices (RDMs) across independent splits of each participant's dataset (average RDM replicability increases from r = 0.46 to r = 0.61). Additionally, we find that GLMdenoise substantially improves pairwise classification accuracy (average classification accuracy increases from 79% correct to 84% correct). We show that GLMdenoise often improves and never degrades performance for individual participants and that GLMdenoise also improves across-participant consistency. We conclude that GLMdenoise is a useful tool that can be routinely used to maximize the amount of information extracted from fMRI activity patterns.

Foreground-Background Segmentation Revealed during Natural Image Viewing.

One of the major challenges in visual neuroscience is represented by foreground-background segmentation. Data from nonhuman primates show that segmentation leads to two distinct, but associated processes: the enhancement of neural activity during figure processing (i.e., foreground enhancement) and the suppression of background-related activity (i.e., background suppression). To study foreground-background segmentation in ecological conditions, we introduce a novel method based on parametric modulation of low-level image properties followed by application of simple computational image-processing models. By correlating the outcome of this procedure with human fMRI activity, measured during passive viewing of 334 natural images, we produced easily interpretable "correlation images" from visual populations. Results show evidence of foreground enhancement in all tested regions, from V1 to lateral occipital complex (LOC), while background suppression occurs in V4 and LOC only. Correlation images derived from V4 and LOC revealed a preserved spatial resolution of foreground textures, indicating a richer representation of the salient part of natural images, rather than a simplistic model of object shape. Our results indicate that scene segmentation occurs during natural viewing, even when individuals are not required to perform any particular task.

A non-invasive, quantitative study of broadband spectral responses in human visual cortex.

Currently, non-invasive methods for studying the human brain do not routinely and reliably measure spike-rate-dependent signals, independent of responses such as hemodynamic coupling (fMRI) and subthreshold neuronal synchrony (oscillations and event-related potentials). In contrast, invasive methods-microelectrode recordings and electrocorticography (ECoG)-have recently measured broadband power elevation in field potentials (~50-200 Hz) as a proxy for locally averaged spike rates. Here, we sought to detect and quantify stimulus-related broadband responses using magnetoencephalography (MEG). Extracranial measurements like MEG and EEG have multiple global noise sources and relatively low signal-to-noise ratios; moreover high frequency artifacts from eye movements can be confounded with stimulus design and mistaken for signals originating from brain activity. For these reasons, we developed an automated denoising technique that helps reveal the broadband signal of interest. Subjects viewed 12-Hz contrast-reversing patterns in the left, right, or bilateral visual field. Sensor time series were separated into evoked (12-Hz amplitude) and broadband components (60-150 Hz). In all subjects, denoised broadband responses were reliably measured in sensors over occipital cortex, even in trials without microsaccades. The broadband pattern was stimulus-dependent, with greater power contralateral to the stimulus. Because we obtain reliable broadband estimates with short experiments (~20 minutes), and with sufficient signal-to-noise to distinguish responses to different stimuli, we conclude that MEG broadband signals, denoised with our method, offer a practical, non-invasive means for characterizing spike-rate-dependent neural activity for addressing scientific questions about human brain function.

Compressive Temporal Summation in Human Visual Cortex.

Combining sensory inputs over space and time is fundamental to vision. Population receptive field models have been successful in characterizing spatial encoding throughout the human visual pathways. A parallel question, how visual areas in the human brain process information distributed over time, has received less attention. One challenge is that the most widely used neuroimaging method, fMRI, has coarse temporal resolution compared with the time-scale of neural dynamics. Here, via carefully controlled temporally modulated stimuli, we show that information about temporal processing can be readily derived from fMRI signal amplitudes in male and female subjects. We find that all visual areas exhibit subadditive summation, whereby responses to longer stimuli are less than the linear prediction from briefer stimuli. We also find fMRI evidence that the neural response to two stimuli is reduced for brief interstimulus intervals (indicating adaptation). These effects are more pronounced in visual areas anterior to V1-V3. Finally, we develop a general model that shows how these effects can be captured with two simple operations: temporal summation followed by a compressive nonlinearity. This model operates for arbitrary temporal stimulation patterns and provides a simple and interpretable set of computations that can be used to characterize neural response properties across the visual hierarchy. Importantly, compressive temporal summation directly parallels earlier findings of compressive spatial summation in visual cortex describing responses to stimuli distributed across space. This indicates that, for space and time, cortex uses a similar processing strategy to achieve higher-level and increasingly invariant representations of the visual world.SIGNIFICANCE STATEMENT Combining sensory inputs over time is fundamental to seeing. Two important temporal phenomena are summation, the accumulation of sensory inputs over time, and adaptation, a response reduction for repeated or sustained stimuli. We investigated these phenomena in the human visual system using fMRI. We built predictive models that operate on arbitrary temporal patterns of stimulation using two simple computations: temporal summation followed by a compressive nonlinearity. Our new temporal compressive summation model captures (1) subadditive temporal summation, and (2) adaptation. We show that the model accounts for systematic differences in these phenomena across visual areas. Finally, we show that for space and time, the visual system uses a similar strategy to achieve increasingly invariant representations of the visual world.

Defining the most probable location of the parahippocampal place area using cortex-based alignment and cross-validation.

The parahippocampal place area (PPA) is a widely studied high-level visual region in the human brain involved in place and scene processing. The goal of the present study was to identify the most probable location of place-selective voxels in medial ventral temporal cortex. To achieve this goal, we first used cortex-based alignment (CBA) to create a probabilistic place-selective region of interest (ROI) from one group of 12 participants. We then tested how well this ROI could predict place selectivity in each hemisphere within a new group of 12 participants. Our results reveal that a probabilistic ROI (pROI) generated from one group of 12 participants accurately predicts the location and functional selectivity in individual brains from a new group of 12 participants, despite between subject variability in the exact location of place-selective voxels relative to the folding of parahippocampal cortex. Additionally, the prediction accuracy of our pROI is significantly higher than that achieved by volume-based Talairach alignment. Comparing the location of the pROI of the PPA relative to published data from over 500 participants, including data from the Human Connectome Project, shows a striking convergence of the predicted location of the PPA and the cortical location of voxels exhibiting the highest place selectivity across studies using various methods and stimuli. Specifically, the most predictive anatomical location of voxels exhibiting the highest place selectivity in medial ventral temporal cortex is the junction of the collateral and anterior lingual sulci. Methodologically, we make this pROI freely available (vpnl.stanford.edu/PlaceSelectivity), which provides a means to accurately identify a functional region from anatomical MRI data when fMRI data are not available (for example, in patient populations). Theoretically, we consider different anatomical and functional factors that may contribute to the consistent anatomical location of place selectivity relative to the folding of high-level visual cortex.

Principles for models of neural information processing.

The goal of cognitive neuroscience is to understand how mental operations are performed by the brain. Given the complexity of the brain, this is a challenging endeavor that requires the development of formal models. Here, I provide a perspective on models of neural information processing in cognitive neuroscience. I define what these models are, explain why they are useful, and specify criteria for evaluating models. I also highlight the difference between functional and mechanistic models, and call attention to the value that neuroanatomy has for understanding brain function. Based on the principles I propose, I proceed to evaluate the merit of recently touted deep neural network models. I contend that these models are promising, but substantial work is necessary (i) to clarify what type of explanation these models provide, (ii) to determine what specific effects they accurately explain, and (iii) to improve our understanding of how they work.

Bottom-up and top-down computations in word- and face-selective cortex.

The ability to read a page of text or recognize a person's face depends on category-selective visual regions in ventral temporal cortex (VTC). To understand how these regions mediate word and face recognition, it is necessary to characterize how stimuli are represented and how this representation is used in the execution of a cognitive task. Here, we show that the response of a category-selective region in VTC can be computed as the degree to which the low-level properties of the stimulus match a category template. Moreover, we show that during execution of a task, the bottom-up representation is scaled by the intraparietal sulcus (IPS), and that the level of IPS engagement reflects the cognitive demands of the task. These results provide an account of neural processing in VTC in the form of a model that addresses both bottom-up and top-down effects and quantitatively predicts VTC responses.

Reward Motivation Enhances Task Coding in Frontoparietal Cortex.

Reward motivation often enhances task performance, but the neural mechanisms underlying such cognitive enhancement remain unclear. Here, we used a multivariate pattern analysis (MVPA) approach to test the hypothesis that motivation-related enhancement of cognitive control results from improved encoding and representation of task set information. Participants underwent two fMRI sessions of cued task switching, the first under baseline conditions, and the second with randomly intermixed reward incentive and no-incentive trials. Information about the upcoming task could be successfully decoded from cue-related activation patterns in a set of frontoparietal regions typically associated with task control. More critically, MVPA classifiers trained on the baseline session had significantly higher decoding accuracy on incentive than non-incentive trials, with decoding improvement mediating reward-related enhancement of behavioral performance. These results strongly support the hypothesis that reward motivation enhances cognitive control, by improving the discriminability of task-relevant information coded and maintained in frontoparietal brain regions.

Resolving Ambiguities of MVPA Using Explicit Models of Representation.

We advocate a shift in emphasis within cognitive neuroscience from multivariate pattern analysis (MVPA) to the design and testing of explicit models of neural representation. With such models, it becomes possible to identify the specific representations encoded in patterns of brain activity and to map them across the brain.