ABSTRACT
Speech brain-computer interfaces (BCIs) have the potential to restore rapid communication to people with paralysis by decoding neural activity evoked by attempted speech into text1,2 or sound3,4. Early demonstrations, although promising, have not yet achieved accuracies sufficiently high for communication of unconstrained sentences from a large vocabulary1-7. Here we demonstrate a speech-to-text BCI that records spiking activity from intracortical microelectrode arrays. Enabled by these high-resolution recordings, our study participant-who can no longer speak intelligibly owing to amyotrophic lateral sclerosis-achieved a 9.1% word error rate on a 50-word vocabulary (2.7 times fewer errors than the previous state-of-the-art speech BCI2) and a 23.8% word error rate on a 125,000-word vocabulary (the first successful demonstration, to our knowledge, of large-vocabulary decoding). Our participant's attempted speech was decoded at 62 words per minute, which is 3.4 times as fast as the previous record8 and begins to approach the speed of natural conversation (160 words per minute9). Finally, we highlight two aspects of the neural code for speech that are encouraging for speech BCIs: spatially intermixed tuning to speech articulators that makes accurate decoding possible from only a small region of cortex, and a detailed articulatory representation of phonemes that persists years after paralysis. These results show a feasible path forward for restoring rapid communication to people with paralysis who can no longer speak.
Subject(s)
Brain-Computer Interfaces , Neural Prostheses , Paralysis , Speech , Humans , Amyotrophic Lateral Sclerosis/physiopathology , Amyotrophic Lateral Sclerosis/rehabilitation , Cerebral Cortex/physiology , Microelectrodes , Paralysis/physiopathology , Paralysis/rehabilitation , VocabularyABSTRACT
BACKGROUND: Brain-computer interfaces can enable communication for people with paralysis by transforming cortical activity associated with attempted speech into text on a computer screen. Communication with brain-computer interfaces has been restricted by extensive training requirements and limited accuracy. METHODS: A 45-year-old man with amyotrophic lateral sclerosis (ALS) with tetraparesis and severe dysarthria underwent surgical implantation of four microelectrode arrays into his left ventral precentral gyrus 5 years after the onset of the illness; these arrays recorded neural activity from 256 intracortical electrodes. We report the results of decoding his cortical neural activity as he attempted to speak in both prompted and unstructured conversational contexts. Decoded words were displayed on a screen and then vocalized with the use of text-to-speech software designed to sound like his pre-ALS voice. RESULTS: On the first day of use (25 days after surgery), the neuroprosthesis achieved 99.6% accuracy with a 50-word vocabulary. Calibration of the neuroprosthesis required 30 minutes of cortical recordings while the participant attempted to speak, followed by subsequent processing. On the second day, after 1.4 additional hours of system training, the neuroprosthesis achieved 90.2% accuracy using a 125,000-word vocabulary. With further training data, the neuroprosthesis sustained 97.5% accuracy over a period of 8.4 months after surgical implantation, and the participant used it to communicate in self-paced conversations at a rate of approximately 32 words per minute for more than 248 cumulative hours. CONCLUSIONS: In a person with ALS and severe dysarthria, an intracortical speech neuroprosthesis reached a level of performance suitable to restore conversational communication after brief training. (Funded by the Office of the Assistant Secretary of Defense for Health Affairs and others; BrainGate2 ClinicalTrials.gov number, NCT00912041.).
Subject(s)
Amyotrophic Lateral Sclerosis , Brain-Computer Interfaces , Dysarthria , Speech , Humans , Male , Middle Aged , Amyotrophic Lateral Sclerosis/complications , Amyotrophic Lateral Sclerosis/rehabilitation , Calibration , Communication Aids for Disabled , Dysarthria/rehabilitation , Dysarthria/etiology , Electrodes, Implanted , Microelectrodes , Quadriplegia/etiology , Quadriplegia/rehabilitationABSTRACT
Theoretical models suggest that executive functions rely on both domain-general and domain-specific processes. Supporting this view, prior brain imaging studies have revealed that executive activations converge and diverge within broadly characterized brain networks. However, the lack of precise anatomical mappings has impeded our understanding of the interplay between domain-general and domain-specific processes. To address this challenge, we used the high-resolution multimodal magnetic resonance imaging approach of the Human Connectome Project to scan participants performing 3 canonical executive tasks: n-back, rule switching, and stop signal. The results reveal that, at the individual level, different executive activations converge within 9 domain-general territories distributed in frontal, parietal, and temporal cortices. Each task exhibits a unique topography characterized by finely detailed activation gradients within domain-general territory shifted toward adjacent resting-state networks; n-back activations shift toward the default mode, rule switching toward dorsal attention, and stop signal toward cingulo-opercular networks. Importantly, the strongest activations arise at multimodal neurobiological definitions of network borders. Matching results are seen in circumscribed regions of the caudate nucleus, thalamus, and cerebellum. The shifting peaks of local gradients at the intersection of task-specific networks provide a novel mechanistic insight into how partially-specialized networks interact with neighboring domain-general territories to generate distinct executive functions.
Subject(s)
Connectome , Executive Function , Humans , Executive Function/physiology , Brain/diagnostic imaging , Brain/physiology , Caudate Nucleus , Attention/physiology , Magnetic Resonance Imaging/methods , Nerve Net/diagnostic imaging , Nerve Net/physiologyABSTRACT
In the human brain, a multiple-demand (MD) network plays a key role in cognitive control, with core components in lateral frontal, dorsomedial frontal and lateral parietal cortex, and multivariate activity patterns that discriminate the contents of many cognitive activities. In prefrontal cortex of the behaving monkey, different cognitive operations are associated with very different patterns of neural activity, while details of a particular stimulus are encoded as small variations on these basic patterns (Sigala et al, 2008). Here, using the advanced fMRI methods of the Human Connectome Project and their 360-region cortical parcellation, we searched for a similar result in MD activation patterns. In each parcel, we compared multivertex patterns for every combination of three tasks (working memory, task-switching, and stop-signal) and two stimulus classes (faces and buildings). Though both task and stimulus category were discriminated in every cortical parcel, the strength of discrimination varied strongly across parcels. The different cognitive operations of the three tasks were strongly discriminated in MD regions. Stimulus categories, in contrast, were most strongly discriminated in a large region of primary and higher visual cortex, and intriguingly, in both parietal and frontal lobe regions adjacent to core MD regions. In the monkey, frontal neurons show a strong pattern of nonlinear mixed selectivity, with activity reflecting specific conjunctions of task events. In our data, however, there was limited evidence for mixed selectivity; throughout the brain, discriminations of task and stimulus combined largely linearly, with a small nonlinear component. In MD regions, human fMRI data recapitulate some but not all aspects of electrophysiological data from nonhuman primates.
Subject(s)
Magnetic Resonance Imaging , Magnetic Resonance Imaging/methods , Humans , Male , Adult , Female , Memory, Short-Term/physiology , Young Adult , Brain/physiology , Brain/diagnostic imaging , Connectome/methods , Photic Stimulation/methods , Brain Mapping/methods , Nerve Net/physiology , Nerve Net/diagnostic imaging , Cognition/physiologyABSTRACT
Adolescence is characterized by the maturation of cortical microstructure and connectivity supporting complex cognition and behavior. Axonal myelination influences brain connectivity during development by enhancing neural signaling speed and inhibiting plasticity. However, the maturational timing of cortical myelination during human adolescence remains poorly understood. Here, we take advantage of recent advances in high-resolution cortical T1w/T2w mapping methods, including principled correction of B1+ transmit field effects, using data from the Human Connectome Project in Development (HCP-D; N = 628, ages 8-21). We characterize microstructural changes relevant to myelination by estimating age-related differences in T1w/T2w throughout the cerebral neocortex from childhood to early adulthood. We apply Bayesian spline models and clustering analysis to demonstrate graded variation in age-dependent cortical T1w/T2w differences that are correlated with the sensorimotor-association (S-A) axis of cortical organization reported by others. In sensorimotor areas, T1w/T2w ratio measures start at high levels at early ages, increase at a fast pace, and decelerate at later ages (18-21). In intermediate multimodal areas along the S-A axis, T1w/T2w starts at intermediate levels and increases linearly at an intermediate pace. In transmodal/paralimbic association areas, T1w/T2w starts at low levels and increases linearly at the slowest pace. These data provide evidence for graded variation of the T1w/T2w ratio along the S-A axis that may reflect cortical myelination changes during adolescence underlying the development of complex information processing and psychological functioning. We discuss the implications of these results as well as caveats in interpreting magnetic resonance imaging (MRI)-based estimates of myelination.SIGNIFICANCE STATEMENT Myelin is a lipid membrane that is essential to healthy brain function. Myelin wraps axons to increase neural signaling speed, enabling complex neuronal functioning underlying learning and cognition. Here, we characterize the developmental timing of myelination across the cerebral cortex during adolescence using a noninvasive proxy measure, T1w/T2w mapping. Our results provide new evidence demonstrating graded variation across the cortex in the timing of T1w/T2w changes during adolescence, with rapid T1w/T2w increases in lower-order sensory areas and gradual T1w/T2w increases in higher-order association areas. This spatial pattern of microstructural brain development closely parallels the sensorimotor-to-association axis of cortical organization and plasticity during ontogeny.
Subject(s)
Connectome , Neocortex , Adolescent , Adult , Bayes Theorem , Child , Humans , Magnetic Resonance Imaging/methods , Myelin Sheath , Young AdultABSTRACT
The Human Connectome Project (HCP)-style surface-based brain MRI analysis is a powerful technique that allows precise mapping of the cerebral cortex. However, the strength of its surface-based analysis has not yet been tested in the older population that often presents with white matter hyperintensities (WMHs) on T2-weighted (T2w) MRI (hypointensities on T1w MRI). We investigated T1-weighted (T1w) and T2w structural MRI in 43 healthy middle-aged to old participants. Juxtacortical WMHs were often misclassified by the default HCP pipeline as parts of the gray matter in T1w MRI, leading to incorrect estimation of the cortical surfaces and cortical metrics. To revert the adverse effects of juxtacortical WMHs, we incorporated the Brain Intensity AbNormality Classification Algorithm into the HCP pipeline (proposed pipeline). Blinded radiologists performed stereological quality control (QC) and found a decrease in the estimation errors in the proposed pipeline. The superior performance of the proposed pipeline was confirmed using an originally-developed automated surface QC based on a large database. Here we showed the detrimental effects of juxtacortical WMHs for estimating cortical surfaces and related metrics and proposed a possible solution for this problem. The present knowledge and methodology should help researchers identify adequate cortical surface biomarkers for aging and age-related neuropsychiatric disorders.
Subject(s)
Brain Diseases , Leukoaraiosis , White Matter , Middle Aged , Humans , White Matter/diagnostic imaging , Aging , Magnetic Resonance Imaging/methods , Cerebral Cortex/diagnostic imaging , Gray Matter/diagnostic imagingABSTRACT
Several cardiovascular and metabolic indicators, such as cholesterol and blood pressure have been associated with altered neural and cognitive health as well as increased risk of dementia and Alzheimer's disease in later life. In this cross-sectional study, we examined how an aggregate index of cardiovascular and metabolic risk factor measures was associated with correlation-based estimates of resting-state functional connectivity (FC) across a broad adult age-span (36-90+ years) from 930 volunteers in the Human Connectome Project Aging (HCP-A). Increased (i.e., worse) aggregate cardiometabolic scores were associated with reduced FC globally, with especially strong effects in insular, medial frontal, medial parietal, and superior temporal regions. Additionally, at the network-level, FC between core brain networks, such as default-mode and cingulo-opercular, as well as dorsal attention networks, showed strong effects of cardiometabolic risk. These findings highlight the lifespan impact of cardiovascular and metabolic health on whole-brain functional integrity and how these conditions may disrupt higher-order network integrity.
Subject(s)
Cardiovascular Diseases , Connectome , Middle Aged , Humans , Aged , Adult , Aged, 80 and over , Connectome/methods , Cross-Sectional Studies , Aging/physiology , Brain/diagnostic imaging , Brain/physiology , Cardiovascular Diseases/diagnostic imaging , Magnetic Resonance ImagingABSTRACT
Recent functional MRI studies identified sensory-biased regions across much of the association cortices and cerebellum. However, their anatomical relationship to multiple-demand (MD) regions, characterized as domain-general due to their coactivation during multiple cognitive demands, remains unclear. For a better anatomical delineation, we used multimodal MRI techniques of the Human Connectome Project to scan subjects performing visual and auditory versions of a working memory (WM) task. The contrast between hard and easy WM showed strong domain generality, with essentially identical patterns of cortical, subcortical, and cerebellar MD activity for visual and auditory materials. In contrast, modality preferences were shown by contrasting easy WM with baseline; most MD regions showed visual preference while immediately adjacent to cortical MD regions, there were interleaved regions of both visual and auditory preference. The results may exemplify a general motif whereby domain-specific regions feed information into and out of an adjacent, integrative MD core.
Subject(s)
Connectome , Visual Perception , Brain/diagnostic imaging , Brain/physiology , Brain Mapping/methods , Humans , Magnetic Resonance Imaging/methods , Memory, Short-Term/physiology , Visual Perception/physiologyABSTRACT
T1-weighted divided by T2-weighted (T1w/T2w) myelin maps were initially developed for neuroanatomical analyses such as identifying cortical areas, but they are increasingly used in statistical comparisons across individuals and groups with other variables of interest. Existing T1w/T2w myelin maps contain radiofrequency transmit field (B1+) biases, which may be correlated with these variables of interest, leading to potentially spurious results. Here we propose two empirical methods for correcting these transmit field biases using either explicit measures of the transmit field or alternatively a 'pseudo-transmit' approach that is highly correlated with the transmit field at 3T. We find that the resulting corrected T1w/T2w myelin maps are both better neuroanatomical measures (e.g., for use in cross-species comparisons), and more appropriate for statistical comparisons of relative T1w/T2w differences across individuals and groups (e.g., sex, age, or body-mass-index) within a consistently acquired study at 3T. We recommend that investigators who use the T1w/T2w approach for mapping cortical myelin use these B1+ transmit field corrected myelin maps going forward.
Subject(s)
Magnetic Resonance Imaging , Myelin Sheath , Bias , Humans , Magnetic Resonance Imaging/methodsABSTRACT
Localising accurate brain regions needs careful evaluation in each experimental species due to their individual variability. However, the function and connectivity of brain areas is commonly studied using a single-subject cranial landmark-based stereotactic atlas in animal neuroscience. Here, we address this issue in a small primate, the common marmoset, which is increasingly widely used in systems neuroscience. We developed a non-invasive multi-modal neuroimaging-based targeting pipeline, which accounts for intersubject anatomical variability in cranial and cortical landmarks in marmosets. This methodology allowed creation of multi-modal templates (MarmosetRIKEN20) including head CT and brain MR images, embedded in coordinate systems of anterior and posterior commissures (AC-PC) and CIFTI grayordinates. We found that the horizontal plane of the stereotactic coordinate was significantly rotated in pitch relative to the AC-PC coordinate system (10 degrees, frontal downwards), and had a significant bias and uncertainty due to positioning procedures. We also found that many common cranial and brain landmarks (e.g., bregma, intraparietal sulcus) vary in location across subjects and are substantial relative to average marmoset cortical area dimensions. Combining the neuroimaging-based targeting pipeline with robot-guided surgery enabled proof-of-concept targeting of deep brain structures with an accuracy of 0.2 mm. Altogether, our findings demonstrate substantial intersubject variability in marmoset brain and cranial landmarks, implying that subject-specific neuroimaging-based localization is needed for precision targeting in marmosets. The population-based templates and atlases in grayordinates, created for the first time in marmoset monkeys, should help bridging between macroscale and microscale analyses.
Subject(s)
Brain Mapping/methods , Brain/anatomy & histology , Callithrix/anatomy & histology , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Anatomic Landmarks , Animals , Brain/surgery , Callithrix/surgery , Equipment Design , Image Processing, Computer-Assisted , Magnetic Resonance Imaging/instrumentation , Reproducibility of Results , Surgery, Computer-Assisted , Tomography, X-Ray Computed/instrumentationABSTRACT
Understanding the amazingly complex human cerebral cortex requires a map (or parcellation) of its major subdivisions, known as cortical areas. Making an accurate areal map has been a century-old objective in neuroscience. Using multi-modal magnetic resonance images from the Human Connectome Project (HCP) and an objective semi-automated neuroanatomical approach, we delineated 180 areas per hemisphere bounded by sharp changes in cortical architecture, function, connectivity, and/or topography in a precisely aligned group average of 210 healthy young adults. We characterized 97 new areas and 83 areas previously reported using post-mortem microscopy or other specialized study-specific approaches. To enable automated delineation and identification of these areas in new HCP subjects and in future studies, we trained a machine-learning classifier to recognize the multi-modal 'fingerprint' of each cortical area. This classifier detected the presence of 96.6% of the cortical areas in new subjects, replicated the group parcellation, and could correctly locate areas in individuals with atypical parcellations. The freely available parcellation and classifier will enable substantially improved neuroanatomical precision for studies of the structural and functional organization of human cerebral cortex and its variation across individuals and in development, aging, and disease.
Subject(s)
Cerebral Cortex/anatomy & histology , Cerebral Cortex/physiology , Neuroanatomy/methods , Adult , Cerebral Cortex/cytology , Connectome , Female , Healthy Volunteers , Humans , Machine Learning , Male , Models, Anatomic , Multimodal Imaging , Neuroimaging , Probability , Reproducibility of Results , Young AdultABSTRACT
Advances in neuroimaging and neuroanatomy have yielded major insights concerning fundamental principles of cortical organization and evolution, thus speaking to how well different species serve as models for human brain function in health and disease. Here, we focus on cortical folding, parcellation, and connectivity in mice, marmosets, macaques, and humans. Cortical folding patterns vary dramatically across species, and individual variability in cortical folding increases with cortical surface area. Such issues are best analyzed using surface-based approaches that respect the topology of the cortical sheet. Many aspects of cortical organization can be revealed using 1 type of information (modality) at a time, such as maps of cortical myelin content. However, accurate delineation of the entire mosaic of cortical areas requires a multimodal approach using information about function, architecture, connectivity, and topographic organization. Comparisons across the 4 aforementioned species reveal dramatic differences in the total number and arrangement of cortical areas, particularly between rodents and primates. Hemispheric variability and bilateral asymmetry are most pronounced in humans, which we evaluated using a high-quality multimodal parcellation of hundreds of individuals. Asymmetries include modest differences in areal size but not in areal identity. Analyses of cortical connectivity using anatomical tracers reveal highly distributed connectivity and a wide range of connection weights in monkeys and mice; indirect measures using functional MRI suggest a similar pattern in humans. Altogether, a multifaceted but integrated approach to exploring cortical organization in primate and nonprimate species provides complementary advantages and perspectives.
ABSTRACT
The goal of our study was to use functional connectivity to map brain function to self-reports of negative emotion. In a large dataset of healthy individuals derived from the Human Connectome Project (N = 652), first we quantified functional connectivity during a negative face-matching task to isolate patterns induced by emotional stimuli. Then, we did the same in a complementary task-free resting state condition. To identify the relationship between functional connectivity in these two conditions and self-reports of negative emotion, we introduce group regularized canonical correlation analysis (GRCCA), a novel algorithm extending canonical correlations analysis to model the shared common properties of functional connectivity within established brain networks. To minimize overfitting, we optimized the regularization parameters of GRCCA using cross-validation and tested the significance of our results in a held-out portion of the data set using permutations. GRCCA consistently outperformed plain regularized canonical correlation analysis. The only canonical correlation that generalized to the held-out test set was based on resting state data (r = 0.175, permutation test p = 0.021). This canonical correlation loaded primarily on Anger-aggression. It showed high loadings in the cingulate, orbitofrontal, superior parietal, auditory and visual cortices, as well as in the insula. Subcortically, we observed high loadings in the globus pallidus. Regarding brain networks, it loaded primarily on the primary visual, orbito-affective and ventral multimodal networks. Here, we present the first neuroimaging application of GRCCA, a novel algorithm for regularized canonical correlation analyses that takes into account grouping of the variables during the regularization scheme. Using GRCCA, we demonstrate that functional connections involving the visual, orbito-affective and multimodal networks are promising targets for investigating functional correlates of subjective anger and aggression. Crucially, our approach and findings also highlight the need of cross-validation, regularization and testing on held out data for correlational neuroimaging studies to avoid inflated effects.
Subject(s)
Anger/physiology , Brain/physiology , Connectome/methods , Facial Recognition/physiology , Fear/physiology , Nerve Net/physiology , Adult , Brain/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging , Male , Nerve Net/diagnostic imaging , Self Report , Social Perception , Young AdultABSTRACT
Research into the human connectome (i.e., all connections in the human brain) with the use of resting state functional MRI has rapidly increased in popularity in recent years, especially with the growing availability of large-scale neuroimaging datasets. The goal of this review article is to describe innovations in functional connectome representations that have come about in the past 8 years, since the 2013 NeuroImage special issue on 'Mapping the Connectome'. In the period, research has shifted from group-level brain parcellations towards the characterization of the individualized connectome and of relationships between individual connectomic differences and behavioral/clinical variation. Achieving subject-specific accuracy in parcel boundaries while retaining cross-subject correspondence is challenging, and a variety of different approaches are being developed to meet this challenge, including improved alignment, improved noise reduction, and robust group-to-subject mapping approaches. Beyond the interest in the individualized connectome, new representations of the data are being studied to complement the traditional parcellated connectome representation (i.e., pairwise connections between distinct brain regions), such as methods that capture overlapping and smoothly varying patterns of connectivity ('gradients'). These different connectome representations offer complimentary insights into the inherent functional organization of the brain, but challenges for functional connectome research remain. Interpretability will be improved by future research towards gaining insights into the neural mechanisms underlying connectome observations obtained from functional MRI. Validation studies comparing different connectome representations are also needed to build consensus and confidence to proceed with clinical trials that may produce meaningful clinical translation of connectome insights.
Subject(s)
Connectome/methods , Brain/diagnostic imaging , Humans , Individuality , Magnetic Resonance Imaging/methods , Nerve Net , NeuroimagingABSTRACT
Social interaction is thought to provide a selection pressure for human intelligence, yet little is known about its neurobiological basis and evolution throughout the primate lineage. Recent advances in neuroimaging have enabled whole brain investigation of brain structure, function, and connectivity in humans and non-human primates (NHPs), leading to a nascent field of comparative connectomics. However, linking social behavior to brain organization across the primates remains challenging. Here, we review the current understanding of the macroscale neural mechanisms of social behaviors from the viewpoint of system neuroscience. We first demonstrate an association between the number of cortical neurons and the size of social groups across primates, suggesting a link between neural information-processing capacity and social capabilities. Moreover, by capitalizing on recent advances in species-harmonized functional MRI, we demonstrate that portions of the mirror neuron system and default-mode networks, which are thought to be important for representation of the other's actions and sense of self, respectively, exhibit similarities in functional organization in macaque monkeys and humans, suggesting possible homologies. With respect to these two networks, we describe recent developments in the neurobiology of social perception, joint attention, personality and social complexity. Together, the Human Connectome Project (HCP)-style comparative neuroimaging, hyperscanning, behavioral, and other multi-modal investigations are expected to yield important insights into the evolutionary foundations of human social behavior.
Subject(s)
Connectome/methods , Neuroimaging/methods , Social Behavior , Animals , Magnetic Resonance Imaging , PrimatesABSTRACT
Many brain imaging studies aim to measure structural connectivity with diffusion tractography. However, biases in tractography data, particularly near the boundary between white matter and cortical grey matter can limit the accuracy of such studies. When seeding from the white matter, streamlines tend to travel parallel to the convoluted cortical surface, largely avoiding sulcal fundi and terminating preferentially on gyral crowns. When seeding from the cortical grey matter, streamlines generally run near the cortical surface until reaching deep white matter. These so-called "gyral biases" limit the accuracy and effective resolution of cortical structural connectivity profiles estimated by tractography algorithms, and they do not reflect the expected distributions of axonal densities seen in invasive tracer studies or stains of myelinated fibres. We propose an algorithm that concurrently models fibre density and orientation using a divergence-free vector field within gyral blades to encourage an anatomically-justified streamline density distribution along the cortical white/grey-matter boundary while maintaining alignment with the diffusion MRI estimated fibre orientations. Using in vivo data from the Human Connectome Project, we show that this algorithm reduces tractography biases. We compare the structural connectomes to functional connectomes from resting-state fMRI, showing that our model improves cross-modal agreement. Finally, we find that after parcellation the changes in the structural connectome are very minor with slightly improved interhemispheric connections (i.e, more homotopic connectivity) and slightly worse intrahemispheric connections when compared to tracers.
Subject(s)
Algorithms , Brain/anatomy & histology , Connectome/methods , Image Processing, Computer-Assisted/methods , White Matter/anatomy & histology , Diffusion Tensor Imaging , HumansABSTRACT
Recent methodological advances in MRI have enabled substantial growth in neuroimaging studies of non-human primates (NHPs), while open data-sharing through the PRIME-DE initiative has increased the availability of NHP MRI data and the need for robust multi-subject multi-center analyses. Streamlined acquisition and analysis protocols would accelerate and improve these efforts. However, consensus on minimal standards for data acquisition protocols and analysis pipelines for NHP imaging remains to be established, particularly for multi-center studies. Here, we draw parallels between NHP and human neuroimaging and provide minimal guidelines for harmonizing and standardizing data acquisition. We advocate robust translation of widely used open-access toolkits that are well established for analyzing human data. We also encourage the use of validated, automated pre-processing tools for analyzing NHP data sets. These guidelines aim to refine methodological and analytical strategies for small and large-scale NHP neuroimaging data. This will improve reproducibility of results, and accelerate the convergence between NHP and human neuroimaging strategies which will ultimately benefit fundamental and translational brain science.
Subject(s)
Brain , Magnetic Resonance Imaging/standards , Neuroimaging/standards , Animals , Brain/anatomy & histology , Brain/diagnostic imaging , Brain/physiology , Echo-Planar Imaging/methods , Echo-Planar Imaging/standards , Functional Neuroimaging/methods , Functional Neuroimaging/standards , Macaca mulatta , Magnetic Resonance Imaging/methods , Neuroimaging/methods , Reproducibility of ResultsABSTRACT
Multi-modal neuroimaging projects such as the Human Connectome Project (HCP) and UK Biobank are advancing our understanding of human brain architecture, function, connectivity, and their variability across individuals using high-quality non-invasive data from many subjects. Such efforts depend upon the accuracy of non-invasive brain imaging measures. However, 'ground truth' validation of connectivity using invasive tracers is not feasible in humans. Studies using nonhuman primates (NHPs) enable comparisons between invasive and non-invasive measures, including exploration of how "functional connectivity" from fMRI and "tractographic connectivity" from diffusion MRI compare with long-distance connections measured using tract tracing. Our NonHuman Primate Neuroimaging & Neuroanatomy Project (NHP_NNP) is an international effort (6 laboratories in 5 countries) to: (i) acquire and analyze high-quality multi-modal brain imaging data of macaque and marmoset monkeys using protocols and methods adapted from the HCP; (ii) acquire quantitative invasive tract-tracing data for cortical and subcortical projections to cortical areas; and (iii) map the distributions of different brain cell types with immunocytochemical stains to better define brain areal boundaries. We are acquiring high-resolution structural, functional, and diffusion MRI data together with behavioral measures from over 100 individual macaques and marmosets in order to generate non-invasive measures of brain architecture such as myelin and cortical thickness maps, as well as functional and diffusion tractography-based connectomes. We are using classical and next-generation anatomical tracers to generate quantitative connectivity maps based on brain-wide counting of labeled cortical and subcortical neurons, providing ground truth measures of connectivity. Advanced statistical modeling techniques address the consistency of both kinds of data across individuals, allowing comparison of tracer-based and non-invasive MRI-based connectivity measures. We aim to develop improved cortical and subcortical areal atlases by combining histological and imaging methods. Finally, we are collecting genetic and sociality-associated behavioral data in all animals in an effort to understand how genetic variation shapes the connectome and behavior.
Subject(s)
Brain/anatomy & histology , Brain/diagnostic imaging , Image Processing, Computer-Assisted/methods , Internationality , Neuroanatomy/methods , Neuroimaging/methods , Animals , Callithrix , Connectome/methods , Connectome/trends , Humans , Image Processing, Computer-Assisted/trends , Macaca mulatta , Neuroanatomy/trends , Neuroimaging/trends , Primates , Species SpecificityABSTRACT
The Human Connectome Project (HCP) was launched in 2010 as an ambitious effort to accelerate advances in human neuroimaging, particularly for measures of brain connectivity; apply these advances to study a large number of healthy young adults; and freely share the data and tools with the scientific community. NIH awarded grants to two consortia; this retrospective focuses on the "WU-Minn-Ox" HCP consortium centered at Washington University, the University of Minnesota, and University of Oxford. In just over 6 years, the WU-Minn-Ox consortium succeeded in its core objectives by: 1) improving MR scanner hardware, pulse sequence design, and image reconstruction methods, 2) acquiring and analyzing multimodal MRI and MEG data of unprecedented quality together with behavioral measures from more than 1100 HCP participants, and 3) freely sharing the data (via the ConnectomeDB database) and associated analysis and visualization tools. To date, more than 27 Petabytes of data have been shared, and 1538 papers acknowledging HCP data use have been published. The "HCP-style" neuroimaging paradigm has emerged as a set of best-practice strategies for optimizing data acquisition and analysis. This article reviews the history of the HCP, including comments on key events and decisions associated with major project components. We discuss several scientific advances using HCP data, including improved cortical parcellations, analyses of connectivity based on functional and diffusion MRI, and analyses of brain-behavior relationships. We also touch upon our efforts to develop and share a variety of associated data processing and analysis tools along with detailed documentation, tutorials, and an educational course to train the next generation of neuroimagers. We conclude with a look forward at opportunities and challenges facing the human neuroimaging field from the perspective of the HCP consortium.
Subject(s)
Connectome/history , Brain/diagnostic imaging , Databases, Factual , Diffusion Magnetic Resonance Imaging , Female , History, 21st Century , Humans , Image Processing, Computer-Assisted , Male , Neuroimaging , Retrospective StudiesABSTRACT
Numerous brain imaging studies identified a domain-general or "multiple-demand" (MD) activation pattern accompanying many tasks and may play a core role in cognitive control. Though this finding is well established, the limited spatial localization provided by traditional imaging methods precluded a consensus regarding the precise anatomy, functional differentiation, and connectivity of the MD system. To address these limitations, we used data from 449 subjects from the Human Connectome Project, with the cortex of each individual parcellated using neurobiologically grounded multimodal MRI features. The conjunction of three cognitive contrasts reveals a core of 10 widely distributed MD parcels per hemisphere that are most strongly activated and functionally interconnected, surrounded by a penumbra of 17 additional areas. Outside cerebral cortex, MD activation is most prominent in the caudate and cerebellum. Comparison with canonical resting-state networks shows MD regions concentrated in the fronto-parietal network but also engaging three other networks. MD activations show modest relative task preferences accompanying strong co-recruitment. With distributed anatomical organization, mosaic functional preferences, and strong interconnectivity, we suggest MD regions are well positioned to integrate and assemble the diverse components of cognitive operations. Our precise delineation of MD regions provides a basis for refined analyses of their functions.