What we can do and what we cannot do with fMRI
TL;DR: An overview of the current state of fMRI is given, and the current understanding of the haemodynamic signals and the constraints they impose on neuroimaging data interpretation are presented.
Abstract: Functional magnetic resonance imaging (fMRI) is currently the mainstay of neuroimaging in cognitive neuroscience. Advances in scanner technology, image acquisition protocols, experimental design, and analysis methods promise to push forward fMRI from mere cartography to the true study of brain organization. However, fundamental questions concerning the interpretation of fMRI data abound, as the conclusions drawn often ignore the actual limitations of the methodology. Here I give an overview of the current state of fMRI, and draw on neuroimaging and physiological data to present the current understanding of the haemodynamic signals and the constraints they impose on neuroimaging data interpretation.
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TL;DR: In this paper, the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI data from 1,000 subjects and a clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex.
Abstract: Information processing in the cerebral cortex involves interactions among distributed areas. Anatomical connectivity suggests that certain areas form local hierarchical relations such as within the visual system. Other connectivity patterns, particularly among association areas, suggest the presence of large-scale circuits without clear hierarchical relations. In this study the organization of networks in the human cerebrum was explored using resting-state functional connectivity MRI. Data from 1,000 subjects were registered using surface-based alignment. A clustering approach was employed to identify and replicate networks of functionally coupled regions across the cerebral cortex. The results revealed local networks confined to sensory and motor cortices as well as distributed networks of association regions. Within the sensory and motor cortices, functional connectivity followed topographic representations across adjacent areas. In association cortex, the connectivity patterns often showed abrupt transitions between network boundaries. Focused analyses were performed to better understand properties of network connectivity. A canonical sensory-motor pathway involving primary visual area, putative middle temporal area complex (MT+), lateral intraparietal area, and frontal eye field was analyzed to explore how interactions might arise within and between networks. Results showed that adjacent regions of the MT+ complex demonstrate differential connectivity consistent with a hierarchical pathway that spans networks. The functional connectivity of parietal and prefrontal association cortices was next explored. Distinct connectivity profiles of neighboring regions suggest they participate in distributed networks that, while showing evidence for interactions, are embedded within largely parallel, interdigitated circuits. We conclude by discussing the organization of these large-scale cerebral networks in relation to monkey anatomy and their potential evolutionary expansion in humans to support cognition.
6,284 citations
TL;DR: It is found that the most common software packages for fMRI analysis (SPM, FSL, AFNI) can result in false-positive rates of up to 70%.
Abstract: The most widely used task functional magnetic resonance imaging (fMRI) analyses use parametric statistical methods that depend on a variety of assumptions. In this work, we use real resting-state data and a total of 3 million random task group analyses to compute empirical familywise error rates for the fMRI software packages SPM, FSL, and AFNI, as well as a nonparametric permutation method. For a nominal familywise error rate of 5%, the parametric statistical methods are shown to be conservative for voxelwise inference and invalid for clusterwise inference. Our results suggest that the principal cause of the invalid cluster inferences is spatial autocorrelation functions that do not follow the assumed Gaussian shape. By comparison, the nonparametric permutation test is found to produce nominal results for voxelwise as well as clusterwise inference. These findings speak to the need of validating the statistical methods being used in the field of neuroimaging.
2,946 citations
Cites methods from "What we can do and what we cannot d..."
...S its beginning more than 20 years ago, functional magnetic resonance imaging (fMRI) (1, 2) has become a popular tool for understanding the human brain, with some 40,000 published papers according to PubMed....
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TL;DR: A plethora of studies will be reviewed on the involvement of long-distance neuronal coherence in cognitive functions such as multisensory integration, working memory, and selective attention, and implications of abnormal neural synchronization are discussed as they relate to mental disorders like schizophrenia and autism.
Abstract: Synchronous rhythms represent a core mechanism for sculpting temporal coordination of neural activity in the brain-wide network. This review focuses on oscillations in the cerebral cortex that occur during cognition, in alert behaving conditions. Over the last two decades, experimental and modeling work has made great strides in elucidating the detailed cellular and circuit basis of these rhythms, particularly gamma and theta rhythms. The underlying physiological mechanisms are diverse (ranging from resonance and pacemaker properties of single cells to multiple scenarios for population synchronization and wave propagation), but also exhibit unifying principles. A major conceptual advance was the realization that synaptic inhibition plays a fundamental role in rhythmogenesis, either in an interneuronal network or in a reciprocal excitatory-inhibitory loop. Computational functions of synchronous oscillations in cognition are still a matter of debate among systems neuroscientists, in part because the notion of regular oscillation seems to contradict the common observation that spiking discharges of individual neurons in the cortex are highly stochastic and far from being clocklike. However, recent findings have led to a framework that goes beyond the conventional theory of coupled oscillators and reconciles the apparent dichotomy between irregular single neuron activity and field potential oscillations. From this perspective, a plethora of studies will be reviewed on the involvement of long-distance neuronal coherence in cognitive functions such as multisensory integration, working memory, and selective attention. Finally, implications of abnormal neural synchronization are discussed as they relate to mental disorders like schizophrenia and autism.
1,774 citations
TL;DR: Neuroimaging and neuropsychological data supply compelling support for the view that a closed-loop circuit represents the major architectural unit of cerebro-cerebellar interactions and provides the cerebellum with the anatomical substrate to influence the control of movement and cognition.
Abstract: Does the cerebellum influence nonmotor behavior? Recent anatomical studies demonstrate that the output of the cerebellum targets multiple nonmotor areas in the prefrontal and posterior parietal cortex, as well as the cortical motor areas. The projections to different cortical areas originate from distinct output channels within the cerebellar nuclei. The cerebral cortical area that is the main target of each output channel is a major source of input to the channel. Thus, a closed-loop circuit represents the major architectural unit of cerebro-cerebellar interactions. The outputs of these loops provide the cerebellum with the anatomical substrate to influence the control of movement and cognition. Neuroimaging and neuropsychological data supply compelling support for this view. The range of tasks associated with cerebellar activation is remarkable and includes tasks designed to assess attention, executive control, language, working memory, learning, pain, emotion, and addiction. These data, along with the revelations about cerebro-cerebellar circuitry, provide a new framework for exploring the contribution of the cerebellum to diverse aspects of behavior.
1,452 citations
Cites background from "What we can do and what we cannot d..."
...…understood, a rough correspondence can often be made between the functional characteristics of a particular cortical area as determined by single-unit recording studies in nonhuman primates, as compared with what has been learned through functional neuroimaging studies in humans (Logothetis 2008)....
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TL;DR: UK Biobank brain imaging is described and results derived from the first 5,000 participants' data release are presented, which have already yielded a rich range of associations between brain imaging and other measures collected by UK Biobanks.
Abstract: Medical imaging has enormous potential for early disease prediction, but is impeded by the difficulty and expense of acquiring data sets before symptom onset. UK Biobank aims to address this problem directly by acquiring high-quality, consistently acquired imaging data from 100,000 predominantly healthy participants, with health outcomes being tracked over the coming decades. The brain imaging includes structural, diffusion and functional modalities. Along with body and cardiac imaging, genetics, lifestyle measures, biological phenotyping and health records, this imaging is expected to enable discovery of imaging markers of a broad range of diseases at their earliest stages, as well as provide unique insight into disease mechanisms. We describe UK Biobank brain imaging and present results derived from the first 5,000 participants' data release. Although this covers just 5% of the ultimate cohort, it has already yielded a rich range of associations between brain imaging and other measures collected by UK Biobank.
1,343 citations
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TL;DR: A new hypothesis about the role of focused attention is proposed, which offers a new set of criteria for distinguishing separable from integral features and a new rationale for predicting which tasks will show attention limits and which will not.
11,452 citations
TL;DR: A summary of the layout of cortical areas associated with vision and with other modalities, a computerized database for storing and representing large amounts of information on connectivity patterns, and the application of these data to the analysis of hierarchical organization of the cerebral cortex are reported on.
Abstract: In recent years, many new cortical areas have been identified in the macaque monkey. The number of identified connections between areas has increased even more dramatically. We report here on (1) a summary of the layout of cortical areas associated with vision and with other modalities, (2) a computerized database for storing and representing large amounts of information on connectivity patterns, and (3) the application of these data to the analysis of hierarchical organization of the cerebral cortex. Our analysis concentrates on the visual system, which includes 25 neocortical areas that are predominantly or exclusively visual in function, plus an additional 7 areas that we regard as visual-association areas on the basis of their extensive visual inputs. A total of 305 connections among these 32 visual and visual-association areas have been reported. This represents 31% of the possible number of pathways if each area were connected with all others. The actual degree of connectivity is likely to be closer to 40%. The great majority of pathways involve reciprocal connections between areas. There are also extensive connections with cortical areas outside the visual system proper, including the somatosensory cortex, as well as neocortical, transitional, and archicortical regions in the temporal and frontal lobes. In the somatosensory/motor system, there are 62 identified pathways linking 13 cortical areas, suggesting an overall connectivity of about 40%. Based on the laminar patterns of connections between areas, we propose a hierarchy of visual areas and of somatosensory/motor areas that is more comprehensive than those suggested in other recent studies. The current version of the visual hierarchy includes 10 levels of cortical processing. Altogether, it contains 14 levels if one includes the retina and lateral geniculate nucleus at the bottom as well as the entorhinal cortex and hippocampus at the top. Within this hierarchy, there are multiple, intertwined processing streams, which, at a low level, are related to the compartmental organization of areas V1 and V2 and, at a high level, are related to the distinction between processing centers in the temporal and parietal lobes. However, there are some pathways and relationships (about 10% of the total) whose descriptions do not fit cleanly into this hierarchical scheme for one reason or another. In most instances, though, it is unclear whether these represent genuine exceptions to a strict hierarchy rather than inaccuracies or uncertainities in the reported assignment.
7,796 citations
TL;DR: The problem of image reconstruction from sensitivity encoded data is formulated in a general fashion and solved for arbitrary coil configurations and k‐space sampling patterns and special attention is given to the currently most practical case, namely, sampling a common Cartesian grid with reduced density.
Abstract: The invention relates to a method of parallel imaging for obtaining images by means of magnetic resonance (MR). The method includes the simultaneous measurement of sets of MR singals by an array of receiver coils, and the reconstruction of individual receiver coil images from the sets of MR signals. In order to reduce the acquisition time, the distance between adjacent phase encoding lines in k-space is increased, compared to standard Fourier imaging, by a non-integer factor smaller than the number of receiver coils. This undersampling gives rise to aliasing artifacts in the individual receiver coil images. An unaliased final image with the same field of view as in standard Fourier imaging is formed from a combination of the individual receiver coil images whereby account is taken of the mutually different spatial sensitivities of the receiver coils at the positions of voxels which in the receiver coil images become superimposed by aliasing. This requires the solution of a linear equation by means of the generalised inverse of a sensitivity matrix. The reduction of the number of phase encoding lines by a non-integer factor compared to standard Fourier imaging provides that different numbers of voxels become superimposed (by aliasing) in different regions of the receiver coil images. This effect can be exploited to shift residual aliasing artifacts outside the area of interest.
6,562 citations
TL;DR: These findings suggest that the BOLD contrast mechanism reflects the input and intracortical processing of a given area rather than its spiking output, and that LFPs yield a better estimate of BOLD responses than the multi-unit responses.
Abstract: Functional magnetic resonance imaging (fMRI) is widely used to study the operational organization of the human brain, but the exact relationship between the measured fMRI signal and the underlying neural activity is unclear. Here we present simultaneous intracortical recordings of neural signals and fMRI responses. We compared local field potentials (LFPs), single- and multi-unit spiking activity with highly spatio-temporally resolved blood-oxygen-level-dependent (BOLD) fMRI responses from the visual cortex of monkeys. The largest magnitude changes were observed in LFPs, which at recording sites characterized by transient responses were the only signal that significantly correlated with the haemodynamic response. Linear systems analysis on a trialby-trial basis showed that the impulse response of the neurovascular system is both animal- and site-specific, and that LFPs yield a better estimate of BOLD responses than the multi-unit responses. These findings suggest that the BOLD contrast mechanism reflects the input and intracortical processing of a given area rather than its spiking output.
6,140 citations
TL;DR: The method can be applied to most laboratory animals in the conscious state and is based on the use of 2‐deoxy‐D‐[14C]glucose as a tracer for the exchange of glucose between plasma and brain and its phosphorylation by hexokinase in the tissues.
Abstract: — A method has been developed for the simultaneous measurement of the rates of glucose consumption in the various structural and functional components of the brain in vivo. The method can be applied to most laboratory animals in the conscious state. It is based on the use of 2-deoxy-D-[14C]glucose ([14C]DG) as a tracer for the exchange of glucose between plasma and brain and its phosphorylation by hexokinase in the tissues. [14C]DG is used because the label in its product, [14C]deoxyglucose-6-phosphate, is essentially trapped in the tissue over the time course of the measurement. A model has been designed based on the assumptions of a steady state for glucose consumption, a first order equilibration of the free [14C]DG pool in the tissue with the plasma level, and relative rates of phosphorylation of [14C]DG and glucose determined by their relative concentrations in the precursor pools and their respective kinetic constants for the hexokinase reaction. An operational equation based on this model has been derived in terms of determinable variables. A pulse of [14C]DG is administered intravenously and the arterial plasma [14C]DG and glucose concentrations monitored for a preset time between 30 and 45min. At the prescribed time, the head is removed and frozen in liquid N2-chilled Freon XII, and the brain sectioned for autoradiography. Local tissue concentrations of [14C]DG are determined by quantitative autoradiography. Local cerebral glucose consumption is calculated by the equation on the basis of these measured values.
The method has been applied to normal albino rats in the conscious state and under thiopental anesthesia. The results demonstrate that the local rates of glucose consumption in the brain fall into two distinct distributions, one for gray matter and the other for white matter. In the conscious rat the values in the gray matter vary widely from structure to structure (54-197 μmol/100 g/min) with the highest values in structures related to auditory function, e.g. medial geniculate body, superior olive, inferior colliculus, and auditory cortex. The values in white matter are more uniform (i.e. 33–40 μmo1/100 g/min) at levels approximately one-fourth to one-half those of gray matter. Heterogeneous rates of glucose consumption are frequently seen within specific structures, often revealing a pattern of cytoarchitecture. Thiopental anesthesia markedly depresses the rates of glucose utilization throughout the brain, particularly in gray matter, and metabolic rate throughout gray matter becomes more uniform at a lower level.
5,988 citations