Elsevier

NeuroImage

Volume 56, Issue 3, 1 June 2011, Pages 1426-1436
NeuroImage

Topographically specific functional connectivity between visual field maps in the human brain

https://doi.org/10.1016/j.neuroimage.2011.02.077Get rights and content

Abstract

Neural activity in mammalian brains exhibits large spontaneous fluctuations whose structure reveals the intrinsic functional connectivity of the brain on many spatial and temporal scales. Between remote brain regions, spontaneous activity is organized into large-scale functional networks. To date, it has remained unclear whether the intrinsic functional connectivity between brain regions scales down to the fine detail of anatomical connections, for example the fine-grained topographic connectivity structure in visual cortex. Here, we show that fMRI signal fluctuations reveal a detailed retinotopically organized functional connectivity structure between the visual field maps of remote areas of the human visual cortex. The structured coherent fluctuations were even preserved in complete darkness when all visual input was removed. While the topographic connectivity structure was clearly visible in within hemisphere connections, the between hemisphere connectivity structure differs for representations along the vertical and horizontal meridian respectively. These results suggest a tight link between spontaneous neural activity and the fine-grained topographic connectivity pattern of the human brain. Thus, intrinsic functional connectivity reflects the detailed connectivity structure of the cortex at a fine spatial scale. It might thus be a valuable tool to complement anatomical studies of the human connectome, which is one of the keys to understand the functioning of the human brain.

Research Highlights

►A novel method is used to estimate topographic functional connectivity structures ►fMRI reveals fine-grained intrinsic functional connectivity structure in humans ►In visual cortex, spontaneous activity is retinotopically structured across areas ►Precise co-fluctuations are observed between V1 and V3 in the absence of any visual input

Introduction

Neurons in the mammalian brain exhibit a large degree of ongoing activity. This spontaneous activity can be observed independent of any sensory input or motor activity. Spontaneous fluctuations are observed on many spatial and temporal scales (Arieli et al., 1996, Fiser et al., 2004, Fox and Raichle, 2007, He et al., 2008, He et al., 2010). Importantly, the intrinsic functional connectivity of cortex can be measured by the correlation structure in spontaneous fluctuations. It has been suggested that the underlying anatomical architecture of the central nervous system shapes the spatial pattern of the intrinsic functional connectivity.

At a fine spatial scale, spontaneous activity has a strong influence on local cortical sensory processing (Arieli et al., 1996, Fiser et al., 2004), and the local intrinsic functional architecture is highly specific and closely matches the functional architecture of visual cortex acquired from sensory evoked activity (Tsodyks et al., 1999). However, it is not known whether such detailed influences are restricted to local cortical circuits or whether a detailed functional connectivity would be evident also if signals from distant cortical regions are considered.

At a coarse spatial scale, there is a large-scale inter-regional correlation structure in the intrinsic functional connectivity of the brain which is evident in spontaneous activity measured with fMRI (Biswal et al., 1995, Fox and Raichle, 2007, Nir et al., 2006, van den Heuvel and Hulshoff Pol, 2010, Vincent et al., 2007, Wang et al., 2008, Zou et al., 2009). Importantly, the functional long-range interactions have been related to large white matter tracts (Greicius et al., 2009, Hagmann et al., 2008, Honey et al., 2009) and follow the known anatomical connectivity patterns in monkeys (Margulies et al., 2009). Based on these findings, intrinsic functional connectivity measured with fMRI was suggested as a ‘tool for human connectomics’ (Van Dijk et al., 2010).

The anatomical connectivity of cortex has been studied on several scales as well. For an overview see Douglas and Martin (2004). On the large scale, cortical connections have mostly been characterized by areal counts of labeled neurons (see e.g., Fellemann and van Essen, 1991). In recent years, diffusion tensor imaging has been employed to measure large axonal bundles between cortical regions in vivo in humans (e.g. Hagmann et al., 2008). On the fine scale, the detailed local cortical microcircuit has been characterized only in few cortical areas and species, for example in cat visual cortex (Binzegger et al., 2004). Further, it has been shown that the distribution of local, horizontal connections is related to functional maps (Bosking et al., 1997), suggesting a tight link between function and local anatomy. Despite the long history of anatomical studies, relatively little is known about how inter-areal anatomical connections precisely align with cortical topographies, in general. However, a visuotopic anatomical connectivity has been demonstrated between visual areas in the monkey (Angelucci et al., 2002, Salin and Bullier, 1995).

Importantly, a large fraction of the synapses onto a cortical neuron are of local origin (Binzegger et al., 2004), while only relatively few synapses are connections from distant cortical areas. This large number of local connections provides the basis for the tight link between spontaneous and evoked activity in local circuits (Tsodyks et al., 1999). However, it is not known whether the relatively few synaptic connections between cortical areas might suffice to shape spontaneous fluctuations in a fine detailed manner even across cortical regions. For example, the intrinsic functional connectivity between topographically organized visual areas might be related to the detailed retinotopic functional organization of the two regions, similar to the anatomical connections in the monkey (Salin and Bullier, 1995).

Here, we used fMRI to measure the fine-grained functional connectivity structure between different topographically organized regions of the human visual cortex. In analogy to visual receptive fields (Dumoulin and Wandell, 2008, Hubel and Wiesel, 1968), we estimate cortico-cortical receptive fields (CCRF) between visual areas V1 and V3, which were then averaged to obtain the topographic connectivity structure (TCS) between the two retinotopic maps. The specific term CCRF of a neuron, or voxel in our case, is in accordance with the concept of a cortical projective field (Sejnowski, 2006). Importantly, we measured the TCS under two fundamentally different conditions: with visual stimulation and without any visual input. The second condition is of particular interest, because the resulting TCS shows the intrinsic functional connectivity and is very likely to reflect the underlying anatomical connectivity. Importantly, the use of fMRI allows us to simultaneously measure activity in distinct topographically organized maps and directly estimating their functional interactions.

Section snippets

Materials and methods

To characterize the spatial structure of functional connectivity between two visual field maps, we measured the linear, spatial filter in a lower visual area (V1) that best predicted activity of a voxel in a higher visual area (V3). In analogy to visual receptive fields (Dumoulin and Wandell, 2008, Hubel and Wiesel, 1968), these topographic connectivity patterns can be regarded as cortico-cortical receptive fields (CCRF, see Fig. 1A). The CCRF were estimated for all voxels in V3 and then

Results

The presentation of the results will focus on the final result of the detailed analysis, i.e. the topographic connectivity structure between retinotopic maps. We will first present the results from experiment S+, where we observe a clear retinotopic structure in line with the visual stimulation. Then the intrinsic TCS measured without any visual input (S−) is presented in detail. The topographic specificity of the TCS is illustrated by several additional analyses, and finally, we compare the

Discussion

The finding of a visuotopic intrinsic functional connectivity structure illustrates that spontaneous fluctuations in brain activity measured with fMRI preserve fine-grained connectivity structures. One might expect a structured functional connectivity under visual stimulation, however for spontaneous fluctuations, measured in complete darkness, this finding is striking. The observed TCS illustrate that fine-grained topographic connectivity whose structure is much more precise than the

Acknowledgments

This work was funded by the Bernstein Computational Neuroscience Program of the German Federal Ministry of Education and Research (BMBF Grant 01GQ0411), the Excellence Initiative of the German Federal Ministry of Education and Research (DFG Grant GSC86/1-2009) and the Max Planck Society.

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