D. C. Van Essen

Intrinsic functional architecture in the anaesthetized monkey brain.

The traditional approach to studying brain function is to measure physiological responses to controlled sensory, motor and cognitive paradigms. However, most of the brain’s energy consumption is devoted to ongoing metabolic activity not clearly associated with any particular stimulus or behaviour. Functional magnetic resonance imaging studies in humans aimed at understanding this ongoing activity have shown that spontaneous fluctuations of the blood-oxygen-level-dependent signal occur continuously in the resting state. In humans, these fluctuations are temporally coherent within widely distributed cortical systems that recapitulate the functional architecture of responses evoked by experimentally administered tasks. Here, we show that the same phenomenon is present in anaesthetized monkeys even at anaesthetic levels known to induce profound loss of consciousness. We specifically demonstrate coherent spontaneous fluctuations within three well known systems (oculomotor, somatomotor and visual) and the ‘default’ system, a set of brain regions thought by some to support uniquely human capabilities. Our results indicate that coherent system fluctuations probably reflect an evolutionarily conserved aspect of brain functional organization that transcends levels of consciousness.

The connections of the middle temporal visual area (MT) and their relationship to a cortical hierarchy in the macaque monkey

The cortical and subcortical connections of the middle temporal visual area (MT) of the macaque monkey were investigated using combined injections of [3H]proline and horseradish peroxidase within MT. Cortical connections were assigned to specific visual areas on the basis of their relationship to the pattern of interhemispheric connections, revealed by staining for degeneration following callosal transection. MT was shown to be reciprocally connected with many topographically organized cortical visual areas, including V1, V2, V3, and V4. These pathways link regions representing corresponding portions of the visual field in the different areas. In addition, MT has reciprocal connections with two previously unidentified cortical areas, which we have designated the medial superior temporal area (MST) and the ventral intraparietal area (VIP). The laminar distribution of terminals and cell bodies in cortical areas connected with MT follows a consistent pattern. In areas V1, V2, and V3, the projections to MT arise largely or exclusively from cells in supragranular layers, and the reciprocal connections from MT terminate mainly in supragranular and infragranular layers. In contrast, the projections to MST and VIP terminate mainly in layer IV, and the reciprocal pathways originate from cells in both superficial and deep layers. On the basis of this pattern, each connection can be designated as forward or feedback in nature, and a hierarchical arrangement of visual areas can be determined. In this hierarchy, MT is at a higher level than V1, V2, and V3, and at a lower level than MST and VIP. Subcortical projections were seen from MT to the claustrum, the putamen, the caudate nucleus, the inferior and lateral subdivisions of the pulvinar complex, the ventral lateral geniculate nucleus, the reticular nucleus of the thalamus, the superior colliculus, and the pontine nuclei.

Concurrent processing streams in monkey visual cortex.

Abstract The concept of multiple processing streams has emerged as a major theme in many studies of the primate visual system. However, the perception of basic attributes such as color, form, depth, and movement cannot be mapped onto different neuronal pathways as a set of simple, one-to-one relationships. Rather, we suggest that many aspects of perception involve significant overlap across a number of paths and cortical areas. Anatomical divergences and convergences that have been reported among processing streams may be related to the multiplicity of strategies for deriving perceptual attributes from the low-level cues provided by retinal images.

Polyneuronal innervation of skeletal muscle in new‐born rats and its elimination during maturation.

1. The events taking place during the elimination of polyneuronal innervation in the soleus muscle of new‐born rats have been studied using a combination of electrophysiological and anatomical techniques. 2. Each immature muscle fibre is supplied by two or more motor axons which converge on to a single end‐plate. There was no sign of electrical coupling between muscle fibres receiving multiple synaptic inputs. By the end of the second week after birth virtually all muscle fibres are innervated by only a single motor axon. 3. The average tension produced by individual motor units, measured in terms of the percentage of the total muscle twitch tension, declined dramatically during the first 2 weeks after birth. During this period there was no significant change in the number of motor neurones innervating the soleus muscle. Thus, the disappearance of polyneuronal innervation reflects a decrease in the number of peripheral synapses made by each motor neurone. 4. The decline in motor unit size was delayed, but not ultimately prevented, by the early surgical removal of all but a few motor axons to the soleus muscle. This procedure also caused a delay in the removal of polyneuronal innervation involving the remaining motor units. 5. Following a crush of the soleus nerve in neonatal animals, regenerating axons usually returned to the original end‐plates. Polyneuronal innervation was extensive at early stages of re‐innervation and it disappeared during the second week after birth just as in normal muscles. 6. Cross‐innervation of neonatal muscles by an implanted foreign nerve caused a rapid disappearance of cholinesterase at denervated original end‐plates and in most fibres prevented re‐innervation by the original nerve. In the small proportion of fibres that did become innervated through both the foreign and original nerves the end‐plates were more than 1 mm apart, and both foreign and original nerve end‐plates could persist indefinitely. 7. Many cross‐innervated fibres received multiple inputs through the foreign nerve. Some foreign end‐plates were separated by distances ranging up to 1 mm. Polyneuronal innervation through the foreign nerve was completely eliminated during maturation but over a slightly longer period than in normal muscles. Apparently the elimination process can act over a distance up to but not much more than 1 mm. 8. These observations suggest that there are several factors influencing the elimination of redundant inputs in immature muscles. Individual motor neurones appear to have an inherent tendency to withdraw the majority of their original complement of peripheral terminals. The determination of which particular synapses are to survive, however, seems to be made in the periphery by a selection among all the synapses that innervate a limited region of each muscle fibre. There may be a competitive interaction among synapses in which those belonging to smaller motor units are less likely to be eliminated, thereby leading to a relatively uniform size of the motor units in the soleus.

The Human Connectome Project: A data acquisition perspective

The Human Connectome Project (HCP) is an ambitious 5-year effort to characterize brain connectivity and function and their variability in healthy adults. This review summarizes the data acquisition plans being implemented by a consortium of HCP investigators who will study a population of 1200 subjects (twins and their non-twin siblings) using multiple imaging modalities along with extensive behavioral and genetic data. The imaging modalities will include diffusion imaging (dMRI), resting-state fMRI (R-fMRI), task-evoked fMRI (T-fMRI), T1- and T2-weighted MRI for structural and myelin mapping, plus combined magnetoencephalography and electroencephalography (MEG/EEG). Given the importance of obtaining the best possible data quality, we discuss the efforts underway during the first two years of the grant (Phase I) to refine and optimize many aspects of HCP data acquisition, including a new 7T scanner, a customized 3T scanner, and improved MR pulse sequences.

Resting-state fMRI in the Human Connectome Project

Resting-state functional magnetic resonance imaging (rfMRI) allows one to study functional connectivity in the brain by acquiring fMRI data while subjects lie inactive in the MRI scanner, and taking advantage of the fact that functionally related brain regions spontaneously co-activate. rfMRI is one of the two primary data modalities being acquired for the Human Connectome Project (the other being diffusion MRI). A key objective is to generate a detailed in vivo mapping of functional connectivity in a large cohort of healthy adults (over 1000 subjects), and to make these datasets freely available for use by the neuroimaging community. In each subject we acquire a total of 1h of whole-brain rfMRI data at 3 T, with a spatial resolution of 2×2×2 mm and a temporal resolution of 0.7s, capitalizing on recent developments in slice-accelerated echo-planar imaging. We will also scan a subset of the cohort at higher field strength and resolution. In this paper we outline the work behind, and rationale for, decisions taken regarding the rfMRI data acquisition protocol and pre-processing pipelines, and present some initial results showing data quality and example functional connectivity analyses.

Functional connectomics from resting-state fMRI.

Spontaneous fluctuations in activity in different parts of the brain can be used to study functional brain networks. We review the use of resting-state functional MRI (rfMRI) for the purpose of mapping the macroscopic functional connectome. After describing MRI acquisition and image-processing methods commonly used to generate data in a form amenable to connectomics network analysis, we discuss different approaches for estimating network structure from that data. Finally, we describe new possibilities resulting from the high-quality rfMRI data being generated by the Human Connectome Project and highlight some upcoming challenges in functional connectomics.

A Weighted and Directed Interareal Connectivity Matrix for Macaque Cerebral Cortex

Retrograde tracer injections in 29 of the 91 areas of the macaque cerebral cortex revealed 1,615 interareal pathways, a third of which have not previously been reported. A weight index (extrinsic fraction of labeled neurons [FLNe]) was determined for each area-to-area pathway. Newly found projections were weaker on average compared with the known projections; nevertheless, the 2 sets of pathways had extensively overlapping weight distributions. Repeat injections across individuals revealed modest FLNe variability given the range of FLNe values (standard deviation <1 log unit, range 5 log units). The connectivity profile for each area conformed to a lognormal distribution, where a majority of projections are moderate or weak in strength. In the G29 × 29 interareal subgraph, two-thirds of the connections that can exist do exist. Analysis of the smallest set of areas that collects links from all 91 nodes of the G29 × 91 subgraph (dominating set analysis) confirms the dense (66%) structure of the cortical matrix. The G29 × 29 subgraph suggests an unexpectedly high incidence of unidirectional links. The directed and weighted G29 × 91 connectivity matrix for the macaque will be valuable for comparison with connectivity analyses in other species, including humans. It will also inform future modeling studies that explore the regularities of cortical networks.

Function in the human connectome: task-fMRI and individual differences in behavior.

The primary goal of the Human Connectome Project (HCP) is to delineate the typical patterns of structural and functional connectivity in the healthy adult human brain. However, we know that there are important individual differences in such patterns of connectivity, with evidence that this variability is associated with alterations in important cognitive and behavioral variables that affect real world function. The HCP data will be a critical stepping-off point for future studies that will examine how variation in human structural and functional connectivity play a role in adult and pediatric neurological and psychiatric disorders that account for a huge amount of public health resources. Thus, the HCP is collecting behavioral measures of a range of motor, sensory, cognitive and emotional processes that will delineate a core set of functions relevant to understanding the relationship between brain connectivity and human behavior. In addition, the HCP is using task-fMRI (tfMRI) to help delineate the relationships between individual differences in the neurobiological substrates of mental processing and both functional and structural connectivity, as well as to help characterize and validate the connectivity analyses to be conducted on the structural and functional connectivity data. This paper describes the logic and rationale behind the development of the behavioral, individual difference, and tfMRI batteries and provides preliminary data on the patterns of activation associated with each of the fMRI tasks, at both group and individual levels.

Cell structure and function in the visual cortex of the cat

1. The organization of the visual cortex was studied with a technique that allows one to determine the physiology and morphology of individual cells. Micro‐electrodes filled with the fluorescent dye Procion yellow were used to record intracellularly from cells in area 17 of the cat. The visual receptive field of each neurone was classified as simple, complex, or hypercomplex, and the cell was then stained by the iontophoretic injection of dye.