Phase-encoded fMRI tracks down brainstorms of natural language processing with subsecond precision.

Natural language processing unfolds information overtime as spatially separated, multimodal, and interconnected neural processes. Existing noninvasive subtraction-based neuroimaging techniques cannot simultaneously achieve the spatial and temporal resolutions required to visualize ongoing information flows across the whole brain. Here we have developed rapid phase-encoded designs to fully exploit the temporal information latent in functional magnetic resonance imaging data, as well as overcoming scanner noise and head-motion challenges during overt language tasks. We captured real-time information flows as coherent hemodynamic waves traveling over the cortical surface during listening, reading aloud, reciting, and oral cross-language interpreting tasks. We were able to observe the timing, location, direction, and surge of traveling waves in all language tasks, which were visualized as "brainstorms" on brain "weather" maps. The paths of hemodynamic traveling waves provide direct evidence for dual-stream models of the visual and auditory systems as well as logistics models for crossmodal and cross-language processing. Specifically, we have tracked down the step-by-step processing of written or spoken sentences first being received and processed by the visual or auditory streams, carried across language and domain-general cognitive regions, and finally delivered as overt speeches monitored through the auditory cortex, which gives a complete picture of information flows across the brain during natural language functioning. PRACTITIONER POINTS: Phase-encoded fMRI enables simultaneous imaging of high spatial and temporal resolution, capturing continuous spatiotemporal dynamics of the entire brain during real-time overt natural language tasks. Spatiotemporal traveling wave patterns provide direct evidence for constructing comprehensive and explicit models of human information processing. This study unlocks the potential of applying rapid phase-encoded fMRI to indirectly track the underlying neural information flows of sequential sensory, motor, and high-order cognitive processes.

Phase-encoded fMRI tracks down brainstorms of natural language processing with sub-second precision.

The human language system interacts with cognitive and sensorimotor regions during natural language processing. However, where, when, and how these processes occur remain unclear. Existing noninvasive subtraction-based neuroimaging techniques cannot simultaneously achieve the spatial and temporal resolutions required to visualize ongoing information flows across the whole brain. Here we have developed phase-encoded designs to fully exploit the temporal information latent in functional magnetic resonance imaging (fMRI) data, as well as overcoming scanner noise and head-motion challenges during overt language tasks. We captured neural information flows as coherent waves traveling over the cortical surface during listening, reciting, and oral cross-language interpreting. The timing, location, direction, and surge of traveling waves, visualized as 'brainstorms' on brain 'weather' maps, reveal the functional and effective connectivity of the brain in action. These maps uncover the functional neuroanatomy of language perception and production and motivate the construction of finer-grained models of human information processing.

High-resolution quantitative and functional MRI indicate lower myelination of thin and thick stripes in human secondary visual cortex.

The characterization of cortical myelination is essential for the study of structure-function relationships in the human brain. However, knowledge about cortical myelination is largely based on post-mortem histology, which generally renders direct comparison to function impossible. The repeating pattern of pale-thin-pale-thick stripes of cytochrome oxidase (CO) activity in the primate secondary visual cortex (V2) is a prominent columnar system, in which histology also indicates different myelination of thin/thick versus pale stripes. We used quantitative magnetic resonance imaging (qMRI) in conjunction with functional magnetic resonance imaging (fMRI) at ultra-high field strength (7 T) to localize and study myelination of stripes in four human participants at sub-millimeter resolution in vivo. Thin and thick stripes were functionally localized by exploiting their sensitivity to color and binocular disparity, respectively. Resulting functional activation maps showed robust stripe patterns in V2 which enabled further comparison of quantitative relaxation parameters between stripe types. Thereby, we found lower longitudinal relaxation rates (R1) of thin and thick stripes compared to surrounding gray matter in the order of 1-2%, indicating higher myelination of pale stripes. No consistent differences were found for effective transverse relaxation rates (R2*). The study demonstrates the feasibility to investigate structure-function relationships in living humans within one cortical area at the level of columnar systems using qMRI.

Topological Maps and Brain Computations From Low to High.

We first briefly summarize data from microelectrode studies on visual maps in non-human primates and other mammals, and characterize differences among the features of the approximately topological maps in the three main sensory modalities. We then explore the almost 50% of human neocortex that contains straightforward topological visual, auditory, and somatomotor maps by presenting a new parcellation as well as a movie atlas of cortical area maps on the FreeSurfer average surface, fsaverage. Third, we review data on moveable map phenomena as well as a recent study showing that cortical activity during sensorimotor actions may involve spatially locally coherent traveling wave and bump activity. Finally, by analogy with remapping phenomena and sensorimotor activity, we speculate briefly on the testable possibility that coherent localized spatial activity patterns might be able to 'escape' from topologically mapped cortex during 'serial assembly of content' operations such as scene and language comprehension, to form composite 'molecular' patterns that can move across some cortical areas and possibly return to topologically mapped cortex to generate motor output there.

Cortical GABA levels are reduced in young adult binge drinkers: Association with recent alcohol consumption and sex.

Binge drinking refers to a pattern of alcohol intake that raises blood alcohol concentration to or above legal intoxication levels. It is common among young adults and is associated with health risks that scale up with alcohol intake. Acute intoxication depresses neural activity via complex signaling mechanisms by enhancing inhibition mediated by gamma-amino butyric acid (GABA), and by decreasing excitatory glutamatergic effects. Evidence primarily rooted in animal research indicates that the brain compensates for the acute depressant effects under the conditions of habitual heavy use. These neuroadaptive changes are reflected in neural hyperexcitability via downregulated inhibitory signaling, which becomes apparent as withdrawal symptoms. However, human evidence on the compensatory reduction in GABA signaling is scant. The neurochemical aspect of this mechanistic model was evaluated in the present study with proton magnetic resonance spectroscopy (1H-MRS) which is sensitive to GABA plus macromolecule signal (GABA + ). Furthermore, we examined sex differences in GABA + levels as a function of a recent history of binge drinking, given interactions between endogenous neurosteroids, GABA signaling, and alcohol. The study recruited young adult women and men (22.2 ± 2.8 years of age) who were classified as binge drinkers (BDs, N = 52) if they reported ≥ 5 binge episodes in the previous six months. Light drinkers (LDs, N = 49) reported drinking regularly, but not exceeding ≤ 2 binge episodes in the past six months. GABA-edited 1H-MR spectra were acquired from the occipital cortex at 3 T with the MEGA-PRESS sequence. GABA + signal was analyzed relative to water and total creatine (Cr) levels as a function of binge drinking history and sex. Controlling for within-voxel tissue composition, both GABA + indices showed decreased GABA + levels in BDs relative to LDs. The reduced GABA + concentration was associated with occasional high-intensity drinking in the BD group. This evidence is consistent with compensatory GABA downregulation that accompanies alcohol misuse, tipping the excitation/inhibition balance towards hyperexcitability. Analysis of the time course of GABA + neuroplasticity indicated that GABA + was lowest when measured one day after the last drinking occasion in BDs. While the BD vs LD differences were primarily driven by LD women, there was no interaction between Sex and a history of binge drinking. GABA + was higher in LD women compared to LD men. Aligned with the allostasis model, the mechanistic compensatory GABA downregulation observed in young emerging adults engaging in occasional binge drinking complements direct neural measures of hyperexcitability in BDs. Notably, these results suggest that neuroadaptation to alcohol is detectable at the levels of consumption that are within a normative range, and may contribute to adverse health outcomes.

Inferior Occipital Gyrus Is Organized along Common Gradients of Spatial and Face-Part Selectivity.

The ventral visual stream of the human brain is subdivided into patches with categorical stimulus preferences, like faces or scenes. However, the functional organization within these areas is less clear. Here, we used functional magnetic resonance imaging and vertex-wise tuning models to independently probe spatial and face-part preferences in the inferior occipital gyrus (IOG) of healthy adult males and females. The majority of responses were well explained by Gaussian population tuning curves for both retinotopic location and the preferred relative position within a face. Parameter maps revealed a common gradient of spatial and face-part selectivity, with the width of tuning curves drastically increasing from posterior to anterior IOG. Tuning peaks clustered more idiosyncratically but were also correlated across maps of visual and face space. Preferences for the upper visual field went along with significantly increased coverage of the upper half of the face, matching recently discovered biases in human perception. Our findings reveal a broad range of neural face-part selectivity in IOG, ranging from narrow to "holistic." IOG is functionally organized along this gradient, which in turn is correlated with retinotopy.SIGNIFICANCE STATEMENT Brain imaging has revealed a lot about the large-scale organization of the human brain and visual system. For example, occipital cortex contains map-like representations of the visual field, while neurons in ventral areas cluster into patches with categorical preferences, like faces or scenes. Much less is known about the functional organization within these areas. Here, we focused on a well established face-preferring area-the inferior occipital gyrus (IOG). A novel neuroimaging paradigm allowed us to map the retinotopic and face-part tuning of many recording sites in IOG independently. We found a steep posterior-anterior gradient of decreasing face-part selectivity, which correlated with retinotopy. This suggests the functional role of ventral areas is not uniform and may follow retinotopic "protomaps."

Multiple b-values improve discrimination of cortical gray matter regions using diffusion MRI: an experimental validation with a data-driven approach.

OBJECTIVE: To investigate whether varied or repeated b-values provide better diffusion MRI data for discriminating cortical areas with a data-driven approach. METHODS: Data were acquired from three volunteers at 1.5T with b-values of 800, 1400, 2000 s/mm2 along 64 diffusion-encoding directions. The diffusion signal was sampled from gray matter in seven regions of interest (ROIs). Rotational invariants of the local diffusion profile were extracted as features that characterize local tissue properties. Random forest classification experiments assessed whether classification accuracy improved when data with multiple b-values were used over repeated acquisition of the same (1400 s/mm2) b-value to compare all possible pairs of the seven ROIs. Three data sets from the Human Connectome Project were subjected to similar processing and analysis pipelines in eight ROIs. RESULTS: Three different b-values showed an average improvement in correct classification rates of 5.6% and 4.6%, respectively, in the local and HCP data over repeated measurements of the same b-value. The improvement in correct classification rate reached as high as 16% for individual binary classification experiments between two ROIs. Often using only two of the available three b-values were adequate to make such an improvement in classification rates. CONCLUSION: Acquisitions with varying b-values are more suitable for discriminating cortical areas.

Reconstructing neural representations of tactile space.

Psychophysical experiments have demonstrated large and highly systematic perceptual distortions of tactile space. Such a space can be referred to our experience of the spatial organisation of objects, at representational level, through touch, in analogy with the familiar concept of visual space. We investigated the neural basis of tactile space by analysing activity patterns induced by tactile stimulation of nine points on a 3 × 3 square grid on the hand dorsum using functional magnetic resonance imaging. We used a searchlight approach within pre-defined regions of interests to compute the pairwise Euclidean distances between the activity patterns elicited by tactile stimulation. Then, we used multidimensional scaling to reconstruct tactile space at the neural level and compare it with skin space at the perceptual level. Our reconstructions of the shape of skin space in contralateral primary somatosensory and motor cortices reveal that it is distorted in a way that matches the perceptual shape of skin space. This suggests that early sensorimotor areas critically contribute to the distorted internal representation of tactile space on the hand dorsum.

The human cerebellum has almost 80% of the surface area of the neocortex.

The surface of the human cerebellar cortex is much more tightly folded than the cerebral cortex. It was computationally reconstructed for the first time to the level of all individual folia from multicontrast high-resolution postmortem MRI scans. Its total shrinkage-corrected surface area (1,590 cm2) was larger than expected or previously reported, equal to 78% of the total surface area of the human neocortex. The unfolded and flattened surface comprised a narrow strip 10 cm wide but almost 1 m long. By applying the same methods to the neocortex and cerebellum of the macaque monkey, we found that its cerebellum was relatively much smaller, approximately 33% of the total surface area of its neocortex. This suggests a prominent role for the cerebellum in the evolution of distinctively human behaviors and cognition.

The ventral striatum dissociates information expectation, reward anticipation, and reward receipt.

Do dopaminergic reward structures represent the expected utility of information similarly to a reward? Optimal experimental design models from Bayesian decision theory and statistics have proposed a theoretical framework for quantifying the expected value of information that might result from a query. In particular, this formulation quantifies the value of information before the answer to that query is known, in situations where payoffs are unknown and the goal is purely epistemic: That is, to increase knowledge about the state of the world. Whether and how such a theoretical quantity is represented in the brain is unknown. Here we use an event-related functional MRI (fMRI) task design to disentangle information expectation, information revelation and categorization outcome anticipation, and response-contingent reward processing in a visual probabilistic categorization task. We identify a neural signature corresponding to the expectation of information, involving the left lateral ventral striatum. Moreover, we show a temporal dissociation in the activation of different reward-related regions, including the nucleus accumbens, medial prefrontal cortex, and orbitofrontal cortex, during information expectation versus reward-related processing.

Altered visual population receptive fields in human albinism.

Albinism is a congenital disorder where misrouting of the optic nerves at the chiasm gives rise to abnormal visual field representations in occipital cortex. In typical human development, the left occipital cortex receives retinal input predominantly from the right visual field, and vice-versa. In albinism, there is a more complete decussation of optic nerve fibers at the chiasm, resulting in partial representation of the temporal hemiretina (ipsilateral visual field) in the contralateral hemisphere. In this study, we characterize the receptive field properties for these abnormal representations by conducting detailed fMRI population receptive field mapping in a rare subset of participants with albinism and no ocular nystagmus. We find a nasal bias for receptive field positions in the abnormal temporal hemiretina representation. In addition, by modelling responses to bilateral visual field stimulation in the overlap zone, we found evidence in favor of discrete unilateral receptive fields, suggesting a conservative pattern of spatial selectivity in the presence of abnormal retinal input.

Detectability of cerebellar activity with magnetoencephalography and electroencephalography.

Electrophysiological signals from the cerebellum have traditionally been viewed as inaccessible to magnetoencephalography (MEG) and electroencephalography (EEG). Here, we challenge this position by investigating the ability of MEG and EEG to detect cerebellar activity using a model that employs a high-resolution tessellation of the cerebellar cortex. The tessellation was constructed from repetitive high-field (9.4T) structural magnetic resonance imaging (MRI) of an ex vivo human cerebellum. A boundary-element forward model was then used to simulate the M/EEG signals resulting from neural activity in the cerebellar cortex. Despite significant signal cancelation due to the highly convoluted cerebellar cortex, we found that the cerebellar signal was on average only 30-60% weaker than the cortical signal. We also made detailed M/EEG sensitivity maps and found that MEG and EEG have highly complementary sensitivity distributions over the cerebellar cortex. Based on previous fMRI studies combined with our M/EEG sensitivity maps, we discuss experimental paradigms that are likely to offer high M/EEG sensitivity to cerebellar activity. Taken together, these results show that cerebellar activity should be clearly detectable by current M/EEG systems with an appropriate experimental setup.

Fine-Grained Mapping of Cortical Somatotopies in Chronic Complex Regional Pain Syndrome.

It has long been thought that severe chronic pain conditions, such as complex regional pain syndrome (CRPS), are not only associated with, but even maintained by a reorganization of the somatotopic representation of the affected limb in primary somatosensory cortex (S1). This notion has driven treatments that aim to restore S1 representations in CRPS patients, such as sensory discrimination training and mirror therapy. However, this notion is based on both indirect and incomplete evidence obtained with imaging methods with low spatial resolution. Here, we used fMRI to characterize the S1 representation of the affected and unaffected hand in humans (of either sex) with unilateral CRPS. The cortical area, location, and geometry of the S1 representation of the CRPS hand were largely comparable with those of both the unaffected hand and healthy controls. We found no differential relation between affected versus unaffected hand map measures and clinical measures (pain severity, upper limb disability, disease duration). Thus, if any map reorganization occurs, it does not appear to be directly related to pain and disease severity. These findings compel us to reconsider the cortical mechanisms underlying CRPS and the rationale for interventions that aim to "restore" somatotopic representations to treat pain.SIGNIFICANCE STATEMENT This study shows that the spatial map of the fingers in somatosensory cortex is largely preserved in chronic complex regional pain syndrome (CRPS). These findings challenge the treatment rationale for restoring somatotopic representations in complex regional pain syndrome patients.

Unraveling the spatiotemporal brain dynamics during a simulated reach-to-eat task.

The reach-to-eat task involves a sequence of action components including looking, reaching, grasping, and feeding. While cortical representations of individual action components have been mapped in human functional magnetic resonance imaging (fMRI) studies, little is known about the continuous spatiotemporal dynamics among these representations during the reach-to-eat task. In a periodic event-related fMRI experiment, subjects were scanned while they reached toward a food image, grasped the virtual food, and brought it to their mouth within each 16-s cycle. Fourier-based analysis of fMRI time series revealed periodic signals and noise distributed across the brain. Independent component analysis was used to remove periodic or aperiodic motion artifacts. Time-frequency analysis was used to analyze the temporal characteristics of periodic signals in each voxel. Circular statistics was then used to estimate mean phase angles of periodic signals and select voxels based on the distribution of phase angles. By sorting mean phase angles across regions, we were able to show the real-time spatiotemporal brain dynamics as continuous traveling waves over the cortical surface. The activation sequence consisted of approximately the following stages: (1) stimulus related activations in occipital and temporal cortices; (2) movement planning related activations in dorsal premotor and superior parietal cortices; (3) reaching related activations in primary sensorimotor cortex and supplementary motor area; (4) grasping related activations in postcentral gyrus and sulcus; (5) feeding related activations in orofacial areas. These results suggest that phase-encoded design and analysis can be used to unravel sequential activations among brain regions during a simulated reach-to-eat task.

Unexplained Progressive Visual Field Loss in the Presence of Normal Retinotopic Maps.

Lesions of primary visual cortex or its primary inputs typically result in retinotopically localized scotomas. Here we present an individual with unexplained visual field loss and deficits in visual perception in the absence of structural damage to the early visual pathway or lesions in visual cortex. The subject, monocular from an early age, underwent repeated perimetry tests over 8 years demonstrating severe anopia of the lower hemifield, and a clockwise progression of the loss through her upper left visual field. Her visual impairment was evident in a number of standardized tests and psychophysics, especially in tasks assessing spatial integration using illusory contours. However, her intellectual ability was intact and her performance in some other tasks assessing color vision or object detection in scenes was normal. We employed functional magnetic resonance imaging (fMRI), electroretinography and visually evoked potentials. Surprisingly, in contrast to the participant's severe anopia, we found no evidence of abnormal function of her early visual pathways. Specifically, we performed retinotopic mapping using population receptive field (pRF) analysis to map the functional organization of visual cortex in the anopic participant and three control participants on two occasions three and a half years apart. Despite the behavioral visual field loss, her retinotopic maps and pRF parameters in visual areas V1-V3 were qualitatively normal. Further behavioral experiments confirmed that this discrepancy was not trivially explained by the difference between stimuli used for retinotopic mapping and perimetry. Structural T1 scans were normal at both time points, and volumetric analysis of white and gray matter tissue on the segmented T1 volumes did not reveal any abnormalities or deterioration over time. Our findings suggest that normal functional organization of early visual cortex without evident structural damage to the early visual pathway as disclosed by the techniques employed in this study does not necessarily guarantee conscious perception across the visual field.

Modelling the Human Cortex in Three Dimensions.

In cognitive neuroscience, brain-behaviour relationships are usually mapped onto a 2D cortical sheet. Cortical layers are a critical but often ignored third dimension of human cortical function. Improved resolution has put us on the threshold of beginning to image human cognition in three dimensions.

Visual loss alters multisensory face maps in humans.

Topographically organised responses to visual and tactile stimulation are aligned in the ventral intraparietal cortex. The critical biological importance of this region, which is thought to mediate visually guided defensive movements of the head and upper body, suggests that these maps might be hardwired from birth. Here, we investigated whether visual experience is necessary for the creation and positioning of these maps by assessing the representation of tactile stimulation in congenitally and totally blind participants, who had no visual experience, and late and totally blind participants. We used a single-subject approach to the analysis to focus on the potential individual differences in the functional neuroanatomy that might arise from different causes, durations and sensory experiences of visual impairment among participants. The overall results did not show any significant difference between congenitally and late blind participants; however, single-subject trends suggested that visual experience is not necessary to develop topographically organised maps in the intraparietal cortex, whilst losing vision disrupted topographic maps' integrity and organisation. These results discussed in terms of brain plasticity and sensitive periods.

Learning of goal-relevant and -irrelevant complex visual sequences in human V1.

Learning and memory are supported by a network involving the medial temporal lobe and linked neocortical regions. Emerging evidence indicates that primary visual cortex (i.e., V1) may contribute to recognition memory, but this has been tested only with a single visuospatial sequence as the target memorandum. The present study used functional magnetic resonance imaging to investigate whether human V1 can support the learning of multiple, concurrent complex visual sequences involving discontinous (second-order) associations. Two peripheral, goal-irrelevant but structured sequences of orientated gratings appeared simultaneously in fixed locations of the right and left visual fields alongside a central, goal-relevant sequence that was in the focus of spatial attention. Pseudorandom sequences were introduced at multiple intervals during the presentation of the three structured visual sequences to provide an online measure of sequence-specific knowledge at each retinotopic location. We found that a network involving the precuneus and V1 was involved in learning the structured sequence presented at central fixation, whereas right V1 was modulated by repeated exposure to the concurrent structured sequence presented in the left visual field. The same result was not found in left V1. These results indicate for the first time that human V1 can support the learning of multiple concurrent sequences involving complex discontinuous inter-item associations, even peripheral sequences that are goal-irrelevant.

A Digital App to Aid Detection, Monitoring, and Management of Dyslexia in Young Children (DIMMAND): Protocol for a Digital Health and Education Solution.

BACKGROUND: Dyslexia, a specific learning difficulty and a disability as defined in the Equality Act 2010, is a lifelong condition that affects a child from the start of education. Dyslexia is characterized by difficulties in language processing (reading, spelling, and writing) which do not correspond with the child's general intellectual abilities. Although dyslexia cannot be cured, there is a consensus that interventions are more effective and have greater impact the earlier they are administered. Effective interventions start with diagnosis. Currently, formal diagnosis requires an assessment by a dyslexia specialist or educational psychologist. These assessments are expensive and are not easy for a non-specialist teacher or parent to interpret. Consequently, formal assessments are normally performed at a much later age, when interventions are less likely to be effective. Combining the latest in scientific research, expertise of dyslexia practitioners and real-time interactivity facilitated by digital technologies, we aim to provide a cost-effective and convenient solution that focuses on early dyslexia detection and management. OBJECTIVE: We discuss the rationale and protocol for the design and development of a digital health solution aimed at improving the early detection, monitoring and management of dyslexia (DIMMAND) in young children (4-8 years). The primary objective is to create a game-based digital solution aimed at children, parents, and teachers that firstly assesses, then monitors and manages progress in a convenient, cost-effective and private environment. METHODS: The proposed solution will be designed and developed in phases. In the initial phase, the full functional specification of the games that constitute the app will be designed, together with the overall architecture of the solution. Prototype proof-of-concept implementation for few of these games, and commercialization strategies will also be developed. The follow-on phases will see the design implemented into a validated solution. RESULTS: In the initial phase, we worked closely with dyslexia specialists, adult dyslexics, teachers of special-needs children, parents of dyslexic children, and senior dyslexia representatives for large organizations. These interactions provided insights into the range of language difficulties faced by dyslexics, which solutions are used by teachers and professionals, and an overall understanding of the market. We comprehensively defined the ethical, privacy, and data security issues. The detailed design spec of the games, the methodology to be followed to interpret the results, and flow diagrams illustrating how the game screens will be presented was completed. As proof of concept, a few reading, visual, and auditory games were developed and successfully tested by stakeholders on different digital devices. The stakeholders provided regular feedback and confirmed the viability of our game-based solution. CONCLUSIONS: DIMMAND has the potential to provide significant positive health care and economic impact. It is expected to reduce intervention costs, improve dyslexia detection at an early age and aid self-management. REGISTERED REPORT IDENTIFIER: RR1-10.2196/9583.

Microstructural parcellation of the human brain.

The human cerebral cortex is composed of a mosaic of areas thought to subserve different functions. The parcellation of the cortex into areas has a long history and has been carried out using different combinations of structural, connectional, receptotopic, and functional properties. Here we give a brief overview of the history of cortical parcellation, and explore different microstructural properties and analysis techniques that can be used to define the borders between different regions. We show that accounting for the 3D geometry of the highly folded human cortex is especially critical for accurate parcellation. We close with some thoughts on future directions and best practices for combining modalities.