Data on connections between the areas of the cerebral cortex and nuclei of the thalamus are too complicated to analyse with naked intuition. Indeed, the complexity of connection data is one of the major challenges facing neuroanatomy. Recently, systematic methods have been developed and applied to the analysis of the connectivity in the cerebral cortex. These approaches have shed light on the gross organization of the cortical network, have made it possible to test systematically theories of cortical organization, and have guided new electrophysiological studies. This paper extends the approach to investigate the organization of the entire corticothalamic network. An extensive collation of connection tracing studies revealed~1500 extrinsic connections between the cortical areas and thalamic nuclei of the cat cerebral hemisphere. Around 850 connections linked 53 cortical areas with each other, and around 650 connections linked the cortical areas with 42 thalamic nuclei. Non-metric multidimensional scaling, optimal set analysis and non-parametric cluster analysis were used to study global connectivity and the 'place' of individual structures within the overall scheme. Thalamic nuclei and cortical areas were in intimate connectional association. Connectivity defined four major thalamocortical systems. These included three broadly hierarchical sensory or sensory/motor systems (visual and auditory systems and a single system containing both somatosensory and motor structures). The highest stations of these sensory/motor systems were associated with a fourth processing system composed of prefrontal, cingulate, insular and parahippocampal cortex and associated thalamic nuclei (the 'fronto-limbic system'). The association between fronto-limbic and somato-motor systems was particularly close. Empirical neuroanatomy has had tremendous success in tracing the connections that link different regions of the brain. However, individual connection tracing studies focus on the connections of a few brain structures in a few individuals. Therefore, each study describes only a small piece of the connectional architecture of the whole brain. Trying to piece together such data for an accurate overview of brain organization is like trying to solve an intricate jigsaw puzzle. There are many complimentary approaches to help put the jigsaw together. High-quality anatomical studies give us the right pieces. Physiological and behavioural data help show how the pieces fit together. We also think that systematic collation and analysis of connection data are valuable tools to help assemble the puzzle and describe the picture (Young, 1992; Hilgetag et al., 1996; Scannell, 1997) . Preliminary attempts to collate neuronal connection data have already been published for the extrinsic connections linking areas in the cerebral cortices of the cat (Scannell and Young, 1993; Scannell et al., 1995; Scannell, 1997) and the macaque (Pandya and Yeterian, 1985; Felleman and Van Essen, 1991; Young, 1992 Young, , 1993 . Systematic analyses of the data show that the cortical networks of cats and macaques contain three sensory systems and a fourth system, termed the 'fronto-limbic' system, composed of prefrontal, insular, cingulate, perirhinal, retrosplenial and entorhinal cortex and the hippocampal formation (Scannell and Young, 1993; Young, 1993; Scannell et al., 1995; Young et al., 1995a,b). The sensory systems all exhibit a degree of hierarchy, both in terms of laminar origin and termination patterns (Felleman and Van Essen, 1991; Young, 1992; Scannell et al., 1995) and because there is a topological progression with some areas being connectionally close to peripheral input and others being distant from peripheral input. Systematic collation and data analysis have also shown that the simple local wiring rules can account for much of the pattern of cortico-cortical connections in the cat and macaque (Young, 1992; Cherniak, 1994; Scannell et al., 1995; Scannell, 1997) . They have shown that sulci and gyri are arranged in a way that efficiently reduces the volume of the connections in the extrinsic cortico-cortical network (Scannell, 1996 (Scannell, , 1997 Van Essen, 1997) . In addition, systematic analysis of cortical connectivity has had success in guiding electrophysiological investigations of the cat visual system , and in providing simple network models that account for classical str ychnine neuronographic data (Hilgetag et al., 1997a) . It is important to extend the systematic approach to include the thalamus. First, almost all neural signals from the sensory and motor periphery reach the cerebral cortex via the thalamus (e.g. Le Gros Clark, 1932; Jones, 1985) . Second, cortical and thalamic processing are closely co-ordinated (e.g. Le Gros Clark, 1942; Kato, 1990; Guillery, 1995; Contreras et al., 1996; Crick and Koch, 1998) . Consequently, an undue emphasis on the cortical networks ignores much of the machinery that may be responsible for sensory and motor processing (Guillery, 1995). This paper considers the extrinsic connections of both the thalamus and cortex of the cat. Researchers seeking large-scale principles of neuronal organization face, in addition to the 'jigsaw puzzle' problem, sampling bias and random sampling error in the primary neuroanatomical literature. There is a strong bias towards a small number of model structures (e.g. areas 17, 18 and LGN in the case of the cat) for studies on laminar origin and termination patterns, cellular targets, synaptic morphology, physiological function, interindividual variability or development of connections. It is not clear if these structures are representative of the rest of the brain. In contrast, systematic collation, while not free from sampling bias, can yield relatively comprehensive catalogues of the gross cortical connections (Young, 1993; Scannell and Young, 1993; Scannell et al., 1995; Burns, 1997; Scannell et al., 1997, and this paper). Therefore, although lacking much of the richness and detail of the original reports, the approach presented here is unusual in its breadth. We hope that it can compliment the more traditional approaches to neuroanatomy, upon which it is entirely dependent for data. Cerebral Cortex Apr/May 1999;9:277-299; 1047-3211/99/$4.00 The Connectional Organization of the Cortico-thalamic System of the Cat J.W. Scannell, G.A.P.C. Burns, C.C. We are currently extending our collation methods (e.g. http://riposte.usc.edu/NeuroScholar) to emphasize available data on laminar origin and termination patterns, cellular targets, synaptic morphology, physiological function, interindividual variability and development. We intend to apply systematic analysis to these aspects of connectivity as and when data become available for a wider range of connections. Before systematically analysing connection data, it is necessary to produce an accurate catalogue of connections. This step presents major practical problems. The primary data differ in, for example, individual animals, quality, method, anatomist, parcellation and nomenclature. There is considerable variability in the cortical connectivity of individuals, though less so in thalamic connectivity (MacNeil et al., 1997) . Parcellation is difficult, especially in brain regions that lack systematic maps of the sensor y periphery (Colby and Duhamel, 1991) . Furthermore, connection tracing is rarely quantitative, 'interesting' parts of the brain have been studied more than 'boring' parts, and connections are not all the same. Therefore, it is necessary to exercise considerable judgement at this stage of the study. These problems notwithstanding, systematic collation is the only way to produce an explicit summary of known connectivity. The first part of this paper presents such a collation of the connectional neuroanatomy of the cat thalamo-cortico-cortical network. The second part of the paper presents the results of three formal analyses that summarize the thalamo-cortical system's connectional architecture in a relatively compact and comprehensible way. The analyses illustrate the 'place' of individual structures in the global connectional scheme and show global features of the organization of the system that are not apparent on casual inspection of the primary connection data. We hope that both the collation and the analyses will guide new empirical research and test organizational models of the thalamo-cortical network as they have already done in the cortical network
These diseases can be treated by surgical ablation or electric stimulation, which requires both the study of the global connectivity and localization of the place of individual structures within the overall scheme REF .
The Connectional Organization of the Cortico-thalamic System of the Cat
Cerebral cortex
Cerebral cortex
Psychology Medicine