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Article ID: WMC00995 2046-1690

Standardized Digital Mapping Of The Central Connections In Humans

Corresponding Author: Dr. Slobodan Malobabic , Professor of Human Anatomy , Dept. of Anatomy, Faculty of Medicine, Belgrade University , Dr Subotica 4/II , 11 0000

Submitting Author: Dr. Slobodan P Malobabic , Professor of Human Anatomy , Dept. of Anatomy, Faculty of Medicine, Belgrade University , Dr Subotica 4/II , 11 0000

Article ID: WMC00995 Article Type: Original Articles Submitted on:16-Oct-2010, 09:39:54 AM GMT Published on: 16-Oct-2010, 01:42:44 PM GMT Article URL: http://www.webmedcentral.com/article_view/995 Subject Categories:ANATOMY Keywords:Human neuroanatomy, , Presentation, Connections mapping, Nervous pathways, Terminology How to cite the article:Malobabic S . Standardized Digital Mapping Of The Central Nervous System Connections In Humans . WebmedCentral ANATOMY 2010;1(10):WMC00995 Source(s) of Funding: There is not any founding source

Competing Interests: There is not competition of interests related to this article.

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Standardized Digital Mapping Of The Central Nervous System Connections In Humans

Author(s): Malobabic S

Abstract about the connections within the central nervous system (CNS) of vertebrates has been accumulated. In addition to directions of fiber pathways, also the sizes of these fibers, transmitters, actions (e.g. This paper attempts to unite different aspects of excitation- inhibition) and other relevant data were knowledge of both, human neuroanatomists and reported, identified or described. Throughout the neuroinformatics engineers, related to the same neuroscience community, there is a general frustration problem of presentation of human connections. with the volume of data that are generated, and their During the history, until to the end of twentieth century, relative inaccessibility in forms other than narrative presentations of the central nervous system text [1]. The development of graphical visualization connections or pathways in humans were related to tools that enable and enhance scientific interaction technical and printing limitations, as well as to with large-scale databases is the next step in insufficient knowledge and data. Explosion of both, neuroimaging informatics and there is a need for a information technologies and neurosciences, caused next generation visual interaction framework [2]. There fundamental changes of this almost traditional is no established common practice in the situation. Different presentations and different computational neuroscience literature for how to approaches in collecting neuroanatomical data visualize what, or which notation to use [3]. Because resulted in very incoherent systems of data of the lack of a generalizable, computable presentation about central nervous system representation of anatomy, developers of computable connections, which situation itself became now terminologies and ontologies in clinical medicine and additional limiting factor. In this paper we propose a biomedical research represented anatomy from their standardized system of presentation, or better to say, own, more or less divergent, viewpoints resulting in of mapping of nervous pathways in geographical terms. heterogeneity [4]. Unification in theoretical medicine is In order to contain the maximum of information and to necessary for international communication and proper remain practical for use, here described system of exchange of results [5], and data sharing can indirectly presentations of connectivity data should be based on benefit and affect computational neuroscientific tool following principles: 1. presentation of one functional development [2]. system by one basic colour; 2. exactly defined colour However, both in anatomy and in neuroscience, the in RGB (red, green, blue) system for each of “” accurate and uniform way of visual presentation of all in neuronal chain forming a pathway; 3. simplicity in of these data combined, has not yet been established visual presentation with several levels (magnifications) or even proposed. In different texts, including of details presentation; 4. design for use primary in textbooks and monographs, different ways of these computer systems, including the possibility of addition presentations were applied and used. Here we present, of new data (extensibility and adaptability). only as examples (Fig. 1), the illustrations published in In creation of such readable representations that are high quality textbooks from three different periods of capable to be updated effectively, aesthetics also twentieth century [6, 7, 8], and it is obvious the should be considered. Several examples in mapping diversity in graphic forms of presentations of human of motor, sensory and limbic pathways are presented. brain connections. Also, problems present in creation of such one system Fig. 1 are discussed, especially those related to It is easy to understand that the minimal knowledge neuroanatomical terminology, as well as possible about human CNS connections (macro- and solutions which offer new technologies. microconnectivity) and pathways, as well as the Introduction absence of corresponding printing and processing technologies, justified such situation in the past. Current situation with a huge amount of dispersed details about human CNS, different level of their significance and importance, and different potential During the last two centuries large amount of data usage, cannot be synthesized into more coherent

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system of knowledge without adequate system of Necessary are the efforts directed to the creation of presentation, mainly of mapping. The basic language increasingly dynamic, interactive maps of human CNS of neuroscience is neuroanatomy [1], and in pathways that can be manipulated digitally. Also, this neurosciences the term “mapping” was almost proposal could be practical as it was the introduction exclusively related to different procedures of of unique (Nomina Anatomica estimation of functions and connections of cortical and Terminologia Anatomica), more than century ago areas [9], or to a tracer studies in different parts or [see 14, 15]. Great and excellent work in the study of systems of brain [10]. only one, and relatively small part of rat brain (bed During our work in science and in education appeared nucleus of ) [16] illustrates the that different brain systems were presented differently. proportions proposed enterprise. Most known example is that motor projection Below, we first review principles of visualization, pathways are marked usually in red and somatic before giving several examples of what is necessary to sensory systems in blue color. This originates from be illustrated in a neuronal network, followed by early circulation illustrations with arterial flow (as discussion about some aspects of such mapping, and efferent- from the ) in red and venous flow (as potential highlights and problems. afferent- to the heart) in blue color. But increasing knowledge about brain revealed that this, almost Methods symbolic, way of presentations is far than sufficient enough. As illustration of successful but isolated (particular) presentation of only In this paper we consider the standardized use of connections is Figure 2 (reproduced with permission) colours, combined with often used traditional markings from a relatively recent book of Nolte [11]. In this figure of directions of neural connections (circles and lines excitatory connections are shown in the green color with terminal bifurcation) within the central nervous and inhibitory ones in red color, as in traffic regulation. system. Connections belonging to one functional This way is suggestive and reasonable for motor system should be precisely numerically defined always systems (go/stop), but cannot be included in some by one standardized colour (hue), including its wider presentations of neural systems. In nearly different, but also precisely defined tonal range. opposite example, the excitatory connections are Definition of colours in this presentation is within the shown in red, and those considered inhibitory were RGB (red, green, blue) colour model, which is an shown in blue [12]. additive colour model widely used in creating Fig. 2 computer graphics. Proposed RGB system In this paper we consider a new, standardized and corresponds to the existence of 3 types of cone cells potentially universal system of presentation of CNS in human , red, green and blue (primary colours), connections, convenient for integration of different according to their maximal spectral sensitivity [17]. data- bases. This paper is aimed only as an indication Proposed use of RGB system can be even more and definition of the problems which require valuable in the future, when only the information about international organized collaboration of experts and wave length of colours would be sufficient for their high technology. Here proposed presentations of definition, what is different from recently used even connections are only the illustration of what the defined, monitor colours. Disadvantages are in degree potential solution may be and what are the currently of discrimination of colours by human . Our noted problems. The American physicist R. Feynman approach is directly opposite to the approach in image once argued that the history of mathematics is the analysis of biological specimens, and therefore avoids history of improved notation. The less cumbersome the problems and limitations of tresholding, image and notation becomes, the more the mathematician's colour quality, resolution, signal to noise ratio and of mindis freed to leap into new logical spaces. Replace input-output devices [18]. The efforts in imaging 'notation' with' visualization', and it is also true that techniques, image processing and image analysis are scientific progress often follows from new ways of made to identify and separate all possible hues and visualizing problems [13]. Complex ideas are best intensities of colours obtained on staining [18], while conveyed through well-designed illustrations which we determine in advance (standardize) exact definition play an important part in science, and are technical of colour which computer should produce illustrations rather than technical drawings, differing in This proposal includes the exact definition of colour their purposes and thus their appearance [12]. (colour profile), for the first, second, third, fourth, etc. However, ccurrently most neurodatabases are (synapse). The starting point (first neuron) in accessible solely by textual queries [2]. any chain of connections could be marked as the

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darkest one, and that each following, i.e. consecutive Beside now classical designation of red color for neuron, should be in lighter tone of same defined somatic motor systems (corticospinal tract), and of colour. Attached pop- up information box should blue color for somatic sensory systems (spinothalamic contain exact definition of colour, and/or some basic tract), example of connections in limbic system is also neuroanatomical data or links. shown here (Fig. 6). In order to contain the maximum of information and to Corticospinal tract remain practical for use, the system of presentation of The presentation of this descending projection connectivity data should meet following requirements: pathway, extremely simplified here for educational 1. accuracy; 2. clarity and simplicity (allowing no purposes, requires two tones of red colour, presenting confusion), 3. possibility of comparison and upper and lower motoneuron. We propose that the first interchange of data, 4. possibility of addition of new (upper motoneuron) should be darker, than the second data (extensibility and adaptability). Aesthetics is also (lower motoneuron) one (Fig. 3). recommended in creation of such readable Fig. 3. representation that is capable of be updated effectively. Background details or topography (such as levels of The spinothalamic tract as one of somatic sensory , actual position of tract within specific CNS pathways, according to the tradition, generally should structure) are not of primary importance now, but they be presented by blue colour. Its three main neurons have contextual role and can be more elaborated, (peripheral or first one, central or second one, and developed and/or linked in any further computer third or cortical neuron) should be shown in different presentation. variants of blue colour. According to general principles To avoid the information overload in a single figure, it given earlier, first neuron should be presented in was suggested to distribute the information between darkest tone of blue colour. In Figure 3 it is defined several figures, each showing different hierarchical with the numbers of RGB as label (can be used as levels [12]. Provided that network models are specified pop- up box), ensuring that always the same colour at a sufficiently high level of abstraction, future would be used. Next neuron in this chain (pathway) is interactive visualization tools could interactively switch presented in lighter tone of blue colour, also defined between different representations of model aspects by RGB numbers, and third neuron is the lightest one. [12]. Different from the ©Google Earth, which deals (Fig. 4). with only one background (our planet), anatomy deals Figure 4: with individually variable “spaces”, each subject having This presentation is simplified or educational (for its own, specific “cartographic” background. In general medical practice) level. However, it is known computer geographical presentation significant step is that in spinothalamic pathway actually there is not triad transition from one type of symbolic presentation (such of three neurons. For example, within the posterior as cities by circles in large scale charts), to other types horns of spinal cord there is a complex of neurons (not of details presentation in small scale charts (such as only the region known as the gelatinous substance) single houses by squares). Crucial step in use of [19] and the processing of pain impulses generally different magnifications is qualitative change of involves the laminae I- VI [20]. Hence, in more visualized details, from node (neuronal assembly) advanced or even scientific level of presentation, connections topology, toward synaptic interneuronal additional tones of blue colour are to be included in connections. This corresponds in visualization of order to illustrate these local, but significant WWW, to the transition step from network node connections in dorsal horns (Fig. 5). topology to visualization of hardware details. This very Figure 5. advanced step is not necessary in proposed system, Papez circuit and even requires limitation. However, some different As illustration of potential difficulties in realization of levels (zoom) of neuroanatomical precision are also this proposal is given the Papez circuit presentation. considered here, starting from educational level for To present well described and long time known [21] medical students, to more detailed presentations, system of limbic connections, first requirement is to which should correspond to higher magnifications define which colour should be used for limbic system. (larger or smaller scale). We for example (quite arbitrary) propose here the brown colour, and as the starting point of this Results presentation we choose the of (hypothalamus is the main effector region of the limbic system - [22]), and therefore Proposed examples is shown as darkest. Every

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next step is lighter in tone, opening the question if can be international, as it is with Terminologia there are at disposal enough tones of brown colour Anatomica [5]. Anatomical concepts and terms are an which can be seen as clearly different by . integral part of not only anatomy texts and atlases, but Other question arises, whether the “starting point” in of all discourse pertaining to the . neuronal circuits always is easy to be defined. Therefore, a logical and consistent representation of Septo-hippocampal fibers in Fig.6 also are indicated anatomical concepts is a requirement for knowledge as dark, as well as hippocampo-hypothalamic fibers sources in essentially all fields of the biomedical are dark, which after signal processing in septal or sciences [25]. The development of neuroanatomical hippocampal regions can be considered as starting ontologies (or structured vocabularies) for computer fibers. Details of local hippocampal connections (as science applications is not possible without rigorous perforant and alvear paths, mossy fibers, etc.) are not specification of relationships between concepts and presented in this picture, but for presentations terms [26], including the corresponding nervous corresponding to higher magnification (zoom) they system parts. For electronic database good foundation should be kept in mind. is Terminologia Anatomica reflecting experience and Figure 6. knowledge summarizied by generations of anatomists. Human neuroanatomists are convenient not simply to participate, but to be an significant part of such an Discussion project, and not only because anatomy can be considered as the first exact medical field; its terminology is a crucial because effective science To increase the efficiency of neuroscience research, a communication is based on an accurate and carefully system is needed to provide a logical and organized defined vocabulary [15]. Different nomenclatures used means to maintain and distribute data [1]. Complex currently in neuroanatomy to describe the structural systems, as networks of interactive entities, are organization of the nervous system lack the precision. studied through a rapidly increasing mass of data in all There is a need for the development of a commonly domains which share a lot of new and fundamental agreed nomenclature in neuroanatomy and this theoretical questions, what is favourable for fundamental problem hinders the next level of analysis developing the new science of complex systems in an of the nervous system [16]. interdisciplinary way [23]. This requires cooperative Inspiring example for neuroanatomists is long time partnership of researchers from multiple disciplines progress in gradual acceptance of international and maximal level of international cooperation. In anatomical terminologies. The society of human neuroanatomy resultant scientific activity will German-speaking anatomists (Anatomische have to catapult the field of neuroinformatics to center Gesellschaft) created the first Latin anatomical stage [24], and can lead to discoveries of new nomenclature (Basiliensia Nomina Anatomica), relations between previously unrelated parts [16]. approved after 12 years of hard work in 1895 at the There are two main issues in realization of this society meeting in Basel (Switzerland). This work, proposal, the role of human neuroanatomists and continued for a long periods, resulted in Parisiensia understanding of nervous pathways (maps) by the Nomina Anatomica (1955; 1961) and the Nomina informatics engineers. Anatomica (1989) [14, 27]. All this finally resulted in What can be the role of neuroanatomists? the new, updated, simplified and uniform terminology Establishment of terminology in human neuroanatomy (Terminologia Anatomica), containing unique is one of most important prerequsites in realization of identifying number and terms in English and in Latin this project. Since development of science requires the [14, 27]. However, knowledge modelers now continuous adjustment of terminology, that is the recognize that it is very difficult to enforce the use of a reason why it was so important to find a common standard terminology [25]. international language for anatomists [5]. In case of neuroanatomical structural data it is difficult Terminology is a system of terms used in a given to have a rigorous definition of a metric space of such scientific field. Nomenclature is a standardized entities directly [2], but for specific spatial locations, (normalized) system of precisely defined terms, set calculations such as in stereotactic neurosurgery according to certain classification principles and based on Talairach [28], could present individual containing terms created within the scope of morphology. Spatial relationships are not of primary terminology [15]. Professional terminology is common importance in proposed system, because individual place, particularly in the fields of mathematics, variability requires some details which in humans are medicine, veterinary and natural sciences, and its use not yet elucidated. Great variability present in human

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neroanatomy, such as the presence or absence of visualize, understand and navigate a world that is too interthalamic adhaesion, different sulcal patterns etc. large and complex to be seen directly like the Web [29, 30], remains unspecified, which is one factor that [33]. Many partial efforts resulted among others, in constrains the scope of the terminology [25], including electronic atlas database applicable for anatomical the pathways mapping. However, this need has targeting, structure labeling and brain mapping [34]. stimulatory and directional influence for further studies Question of anatomical precision or accuracy is of CNS connections, by generating hypothesis and related to the purpose of the map. For educational ideas for research. level (as for students) less details and main stream of Open question is how many ”subsystems” (or modules) impulses should be sufficient. Practically we propose should be defined in human CNS and whether is creation of system of topological maps (as very possible to each of them to ascribe specific (“their general type of map), which at its first level disregards own”) color. Even if not always color varitations visible scale in the interest of clarity, what corresponds to a by human eye, different RGB numbers (properties) will low magnification map. The level of detail of the be error- free identified by computer. The development connectivity may vary for complex networks where the of maps for anatomical subsystems, such as the number of lines and line-crossings increases, resulting somatosensory or motor systems, is typically driven by in cluttered illustrations [12]. the need to catalogue functional activation studies or For complex or/and specialists studies, as well as for to describe pathways of connectivity [9]. These complex analytical and projecting purposes, detailed subsystems correspond to “organs” in multi- maps including local circuits, collaterals and parallel organ what is the [31]. We can, more or streams should be necessary. Links to other less arbitrary, identify for example, motor systems, databases connected as modules, such as Visible somatic sensory systems, (or only pain system), Human, Connectivity Pattern Tables [12], Brain general senses pathways (visual, acoustic, gustatory, Architecture Knowledge Management System [16] or olfactory, balance), limbic system, central autonomic Foundational Model of Anatomy [4] can be used. network, (different) memory systems, cortical Parallelism of neural networks and internet association systems, cerebellar system, food and Here we discuss some similarities or even analogies in water intake regulatory system(s), etc. Even iff it design and in studies of neural pathways and of seems that there is not „enough“ colors, we assume Internet, as the reason why neuroinfomatics engineers that one (same) tone of one color can be applied in should participate in this project. While the different very complex systems (visual and construction perspective to a large degree builds on participating in memory also) showing that some fibers, terminology from neuroanatomy, the connection view originating from one system diverge, bifurcate or of networks seems to have received little attention in overlap into different pathways. Actually we expect the past, whence there is no established terminology that the main problem of neuroanatomy here will be [12]. The informatics community with the the absence of informations, insufficient informations, unification of existing large, heterogeneous or inadequately processed informations which are neurodatabases in a user-transparent manner, what expected to be mapped in humans. goes above and beyond data sharing, [2] what is very Why “maps”? much like the WWW, where there is an In general, neuroanatomy is in many aspects interconnection of data processing and storage nodes analogous to geography, and it is not only the in a decentralized network. However, an alternate coincidence that in both sciences many data were parallel goal complementing these efforts is the ability presented in printed (graphic) collections (of the earth to graphically navigate, browse and query such or body maps), called Atlases [1,32]. The presentation aggregations of repositories [2]. of CNS pathways in many aspects can use A kind of complex idea (information) which becomes a geographical (cartographic) methods as kind of distinct memorable unit capable of spreading itself is thematic cartography, involving maps of specific called meme [35], and can be stored in , themes oriented toward specific neuroscience computers, etc. [36]. The storage of memes in brain audiences. Like geography, neuroscience requires has a neuroanatomic substrate and is related to accepted maps, terminologies, coordinate systems, synaptic structures, constelation and configurations. and reference spaces to allow accurate and effective Other very powerfull system for storing and spreading communication within the field and with allied memes is the World Wide Web [see in 36]. Term disciplines. Unlike geographic atlases, anatomic mapping is widely used in research of Internet and atlases cannot assume a single, constant physical significant research and technical challenge in the reality [1]. Graphical maps provide a good method to study of large information networks is related to the

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Illustrations

Illustration 1

Fig. 1. CNS pathways. Years: A. 1921 [6]; B. 1946 [7]; C. 1958 [8] (red- touch; blue- pain)

Illustration 2

Fig. 2. Colors as in traffic (red-stop; green-go); Year 2000 [11](permission of Elsevier)

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Illustration 3

Fig. 3. Corticospinal path defined by RGB system numbers ensuring use of standard red color tones

Illustration 4

Fig. 4. Spinothalamic tract, overview. Box indicates posterior horn details magnified in Fig. 5.

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Illustration 5

Fig. 5. Spinothalamic tract (box in Fig. 5). Details analog to light microscopy high magnification

Illustration 6

Fig. 6. Difficulties (Papez circuit): long neuronal chain needs larger color scale

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