EVOLUTION OF THE HUMAN FOREBRAIN
The two fundamental variables defining forebrain evolution are the parameters of phylogenetic age and input specificity. The parameter of phylogenetic age was first quantitatively demonstrated in the marsupial neocortex as the set of “successive waves of circumferential differentiation” (Abbie, 1942). The analogous sequence of age 1evels detected in the cortex of placental mammals by Sanides (1969), were correspondingly designated “growth rings of the neocortex.” The parameter of input specificity is manifest as the parallel series of cortical bands, each of which receives the thalamic relay of a specific forebrain input. Each cortical input band is distinguished according to the various sensory (Penfield & Rasmussen, 1950) or motor (Hassler, 1966) functional responses elicited during localized cortical stimulation.
The exact number of fundamental levels has been accurately determined for both basic forebrain parameters. Sanides (1972) proposed that the human neocortex evolved as a sequence of four concentric growth rings comprising a mediolateral hemisphere gradient. Similarly, the interoceptive, exteroceptive and proprioceptive input categories, each project to its own fourcortical band complex, which taken collectively define an anteroposterior hemisphere gradient. When the paracoronal variable of phylogenetic age is plotted as the ordinate and the parasagittal parameter of input specificity charted as the abscissa in a Cartesian coordinate system, the resulting grid (see Fig. 1) is spatially oriented in strict correspondence to the standard cortical area] representation. Each unit square of the chart depicts the paired coordinate of unique age and input parameter levels.
The areal demarcations of the conventional cortical parcellation schemes coincide strongly with the boundaries interposed between the individual levels of both forebrain parameters. Accordingly, the human cortical parcellation schemes of Brodmann (1909) and of von Economo (1929) correlate topographically well with the theoretically derived parameter grid. Areas of the hemisphere convexity correlate quantitatively on a onetoone basis with the coordinate unit squares. A certain amount of correlative redundancy is, nevertheless, inevitable for the phylogenetically older insular/cingulate cortical regions.
The parallel evolution of both the neocortex and the thalamus dictates that the latter also differentiates as a function of two basic parameters. The anteroposterior series of cortical input bands is oriented in a sequential order matching the corresponding sagittal array of input nuclei in the dorsal thalamus. In addition, Hassler’s (1972) theory of hexapartition of the thalamus according to the criterion of input specificity, is very reminiscent of the corresponding number of growth waves in the neocortex. The equivalent number of parameter levels for both thalamus and cortex, dictates that both of these major subdivisions follow an identical coordinate plot. Accordingly, the human thalamic parcellation scheme of Hassler (1959) correlates topographically, on a one-to-one basis in conjunction with the basic parameter grid. Furthermore, each thalamic nucleus of specific parameter coordinates projects principally to the cortical area of identical paircoordinate values, implying that thalamocortical interconnectivity is also defined in terms of the dual parameter paradigm.
The parameter grid illustrated in Fig. 1 is partially reproduced from a previous journal article by the author (LaMuth, 1977), This modified diagram represents a first attempt at quantitatively ordering subdivisions of the forebrain into a globally coherent pattern. One shortcoming that had detracted from these theoretical determinations has recently been remedied by a further expansion of the dual parameter paradigm. This drawback resulted from attributing the same cytoarchitectonic area to more than a single parameter unitsquare. The forebrain parcellation schemes of Brodmann, von Economo and Hassler have proven too experimentally useful over the years to justify more extensive parcellation schemes. The predominance of redundancies occurring between adjacently paired sequences of unit squares is more than coincidental, This distinct pattern proves to be the key to a new theory of forebrain phylogenesis that differs radically from both the theory proposed by Sanides (1969) and this author’s subsequent critique (LaMuth, 1977).
THE CIRCUMFERENTIAL GROWTH WAVES OF NEOCORTICAL EVOLUTION
The cortical manifestation of the parameter of phylogenetic age is most readily defined in terms of the set of circumferential growth rings of neocortical differentiation portrayed in Fig. 2. According to Sanides (1970), there occur two discrete stages of differentiation in the cortex. The initial lamination of the paleocortical and archaecortical components of the primordial allocortical age level creates the periallocortical growth wave, In the second stage of the differentiation the periallocortex, in turn, generates a sequence of three additional circumferential waves, designated by Sanides as pro, para, and konioage levels and characterized as variations of the hexalaminar organization of the periallocortex rather than additional lamination phases.
Contrary to this theory, however, the final koniocortical growth wave, covering virtually the entire hemisphere convexity, was reevaluated and found to actually be composed of a sequence of two developmentally distinct neocortical growth waves. By cytoarchitectonic criteria it is inconsistent to group the heterotypical classical koniocortex and the homotypic association cortex within the same cortical growth wave. By myelographic standards, koniocortex represents a focal maximum of the hemisphere myelination trend (Sanides, 1969), signifying a phylogenetically later development than the less accentuated association region. According to these basic criteria, Sanides’ final neocortical growth wave is intrinsically modified into a sixth order koniocortical maximum, flanked by a pair of belt zones corresponding to a fifth order growth ring. Retaining the format introduced by Sanides, it is proposed that this distinction be recognized by restricting the term ‘koniocortex’ to the sixth wave of differentiation while coining the term ‘pleurokoniocortex’ to define the ringlike fifth cortical wave.
A REVISION OF NEOCORTICAL URTREND THEORY
Koniocortex is unique among cortical waves, in that it appears as a central core surrounded concentrically by all of the older growth rings. Those portions of the growth rings, positioned between the medial koniocortical border and the archaecortex are termed the medial urtrend, while the growth ring segments, intermediate to the paleo cortex and the lateral koniocortical boundary, are termed the lateral urtrend (Sanides, 1970). Using cytoarchitectonic and myelographic techniques, Sanides demonstrated that the classical sensorimotor representations had developed via continuity across both urtrends; however, with one urtrend being generally more accentuated than its counterpart. The parameter grid shown in Figure l portrays an attempt by the author to apply this principle to all representative areas within the final koniocortical growth core. It is this precise insistence on the existence of an unaccented urtrend, which accounted for the paired redundancies between unit squares of adjacent urtrends. Figure 3 shows the appropriately revised version of the parameter grid, showing each koniocortical representation as a product of a single dominant urtrend.
The jagged line, depicted at the interface between the medial and lateral urtrends of Fig. 3 represents what is termed the urtrend limiting sulcus (Sanides, 1969). This limiting sulcus in man is represented rostrally as the inferior frontal sulcus, intermediately as the sensorimotor sulcus between the arm and head representations and caudally as the interparietal sulcus (Sanides, (1970). The position of each koniocortical representation relative to this limiting sulcus, is a valuable criterion for determining its urtrend of origin. In the frontal lobe, for instance, the inferior frontal gyrus is composed of a sequence of three highly differentiated areas, denoted as pars opercularis (#44), pars triangularis (#45), and pars orbitalis (#12) (Sanides, 1964). Each of these areas characteristically displays giant pyramidal cells in lamina IIIC: an essential property of areal maximums derived across the lateral urtrend. The middle frontal gyrus is host to an analogous sequence of urtrend maxima; areas #46, #8ä, and #6aá. Each of these areas displays a size accentuation of pyramidal cells in lamina V characteristic of their medial urtrend origin.
A close inspection of the posterior association region reveals the presence of a pair of conspicuously myelinated koniocortical bands. The visuoauditory band is situated in area #39 of the visual association region, while the corresponding visuosensory band is located between areas #7 and #40 in the somatosensory association region. These bands were first detected during gross dissection as regions of dramatic myelin accentuation (Smith, 1907). These same cortical strips were subsequently shown to commence myelination much earlier than the surrounding association regions (Flechsig, 1920). The medially derived visuosensory band is located on the dorsal wall of the interparietal sulcus, while the visuoeuditory band is situated lateral to the occipital continuation of this sulcus. The classical visual area #17 was cited by Sanides (1970) as derived solely along a medial urtrend gradient. Accordingly, area #17 exhibits the giant pyramidal cells of Meynert in cortical lamina V. In the same article, Sanides proposed that the classical auditory representation developed solely along a lateral urtrend gradient; at least in the case of lamina IIIc accentuated area #42. Auditory area #41 does not display giant lamina IIIc pyramidal cells, accordingly being derived by way of a medial urtrend gradient spanning the superior temporal gyrus.
The remaining intermediate segment of the koniocortical core is composed of sensorimotor areas #4ă, #3a, and #3b of the pre and postcentral gyri. The distended parallel orientation of all three areas perpendicular to the urtrend limiting sulcus, not only promotes somatotopic crossmodal continuity, but unfortunately invalidates the limiting sulcus as an urtrend determining criterion. Unlike the classical somatosensory area #3b, which displays giant pyramidal cells in lamina IIIc, the cortical motor areas #4ă and #3a exhibit large pyramidal cells in both inner and outer laminae (Bailey & von Bonin, 1951). These latter two areas will be provisionally included as fitting the pattern of strict unit alternation for medially and laterally derived core areas. Here, only single alternate urtrends are prerequisite for koniocortical differentiation, so that the few remaining cortical duplications occur in the primitively differentiated and experimentally inaccessible insular and cingulate gyri.
THE NEOCORTICAL LAMINATION THEORY
In light of the preceding revision of the cortical urtrend theory, a corresponding modification must also be made in Dart’s (1934) theory of the origin of the neocortex. Dart had noted continuity between the archaecortex and the internal cortical laminae on one hand, and between the paleocortex and the external laminae on the other. These observations have been interpreted to be the earliest manifestations of a primordial lamination of the paleocortex over the archaecortex to yield the characteristic hexalaminar organization of the neocortex.
THE THALAMIC GROWTH SHELL THEORY
Mention of the other major subdivision of the forebrain, the dorsal thalamus, was deferred until now in order to exploit the many potential analogies to cortical phylogenesis. The parallel evolution of the dorsal thalamus and neocortex implies the existence of a phylogenetic gradient of diencephalic differentiation homologous to the corresponding age gradation of the telencephalon. The threedimensional organization of the dorsal thalamus, however, renders the diencephalic gradient more difficult to detect than the orderly growth rings of the planar pallium. Hassler’s paradigm of hexapartition of input termination sites in the dorsal thalamus represents the diencephalic counterpart of the six distinct parameter levels demonstrated for the neocortical age gradation. According to Hassler (1972) there occur six distinct thalamic levels, ranked in order of specificity as (1) relay (2) first integrative level (3) second integrative level (4) composite multisensory (5)reticulate feedback, and (6) unspecific protopathic (see Fig. 4).
The primordial unspecific protopathic age level provides the clue for determining the precise mechanism of dorsal thalamic differentiation. The anterior portion of the nonspecific thalamic gray, consisting of the nucleus fasciculosus and reuniens, pars ventralis of nucleus medialis and centralis, and the rostral parts of nucleus parafascicularis and centromedian, has been demonstrated to be of subthalamic origin (ReinosoSuarez, 1966). In the same article, the reticular nucleus of the next most recent age level was cited as an additional derivative of the subthalamus suggesting the existence of a subthalamic gradient of thalamic differentiation. The subthalamus borders the dorsal thalamus from below, dictating that this gradient be termed the ventral urtrend of dorsal thalamic differentiation.
The remaining posterior segment of the unspecific age level includes such subdivisions as the nucleus limitans, suprageniculatus, peripenduncularis and posterior centromedian. This caudal series of nuclei collectively display a distinctively intense cholinesterasic staining activity (Poirer, 1974), denoting a common developmental origin. The close proximity and/or continuity of this posterior series of nuclei to the habaenula (Hassler, 1959) suggests that the epithalamus represents the other fundamental moiety of dorsal thalamic differentiation. At least in lower vertebrates, the epithalamus borders the dorsal thalamus from above, dictating that the corresponding gradient be termed the ‘dorsal urtrend’ of the thalamic differentiation.
The primordial precursors of the dorsal thalamus receive a dual optic projection similar to the dual olfactory bulb projection to the allocortex. More specifically, the epithalamus receives direct visual input from the dorsal parietal eye of lower vertebrates, while the subthalamus is similarly related to the main lateral eyes. The parietal eye of lower vertebrates develops embryologically from the distal end of the pineal or parapineal evagination of the epithalamic ependyma. “In the primative lamprey eel, both pineal and parapineal bodies develop ocular structures, suggesting that a remote ancestral vertebrate had paired dorsal eyes as well as the persistent lateral eyes” (Sarnat and Netsky, 1974). Nerve fibers from the retina of the parietal eye project to the habaenula (Kappers, 1965), however, all photosensory afferents to the habaenula degenerate upon atrophy of the parietal eye in mammals. The primordial visual projection from the paired lateral eyes is directed to the pregeniculate nucleus, which was cited as yet another derivative of the subthalamus (ReinosoSuarez, 1966).
DISCUSSION
The revised edition of the dual parameter grid proves to be a more consistent paradigm for ordering the wealth of experimental findings. The radical elimination of roughly half of the unitsquares of the original parameter grid served only to clarify the theoretical trends involved. The fact that only redundant inconsistencies were eliminated by this revision in both the thalamus and the cortex establishes that the more compact diagram is indeed the closest to experimental reality.
The precise number of component urtrends is also a phylogenetically stable feature for both major forebrain divisions. Both the frontal granular cortex and the dorsomedial thalamic nucleus are each subdivided into four component urtrends, dealing with interoceptive inputs derived from the hypothalamus (Nauta & Haymaker ,l969) and the limbic midbrain area (Guillery, 1959; Massopust & Thompson, 1962). The agranular frontal cortex and the lateral thalamic mass are similarly split four ways each, to deal individually with the variety of proprioceptive inputs reaching the forebrain (see Fig. 4). By taking the developmentally related auditory and somatosensory representations as a unit, the exteroceptivelyoriented posterior granular cortex and pulvinar/geniculate complex also display a four partite organization. This highly stable 444 arrangement makes it highly unlikely that any new urtrends will be added as a result of a more comprehensive parcellation of the forebrain.
The ultimate test of the dual parameter paradigm is based upon the odds of two such widely divergent divisions of the forebrain, both being correlated to the same coordinate system. The cortical relay of each thalamic input category (by way of the thalamic radiations) by definition predicts an equivalent complement of input specificity units in the cortex. The identical number of age levels in both thalamus and cortex, furthermore, suggests that only correspondingly numbered age levels are reciprocally interconnected across the internal capsule. Theoretically, a thalamic cell on a discrete point within the timedifferentiation continuum directs its primary projection to cortical cells derived during the same phylogenetic age. These theoretical restrictions specify that only thalamic and cortical areas of identical age and input coordinates, (i.e. in the same unit square) interconnect via the thalamic radiations. In his classical parcellation treatise on the human thelamus, Hassler (1959) cites a wide assortment of thalamic projections that correlate consistently to the basic parameter grid. Yakolev’s (et al. l966) documentation of the cortical projections of the compositemultisensory thalamic age level, further corroborate the unitsquare, theoretical restrictions. It is this excellent topographical correlation to the basic parameter grid, of both connectivity and parcellation aspects of forebrain organization, that establishes the dual parameter paradigm as a truly accurate account of human forebrain evolution.
SUMMARY
The cytoarchitectonic subdivisions of both the thalamus and the neocortex are topographically defined in terms of the variables of phylogenetic age and input specificity. The cortical and thalamic parcellations of Brodmann, von Economo and Hassler are each quantitatively correlated to a specific Cartesian coordinate value designating discrete levels for both age and input basic parameters. The variable of phylogenetic age is represented in the cortex by the five circumferential growth rings demonstrated by Sanides, plus an additional growth ring detected intermediate to the fifth and sixth age levels and designated as “pleurokoniocortex.” The paleocortex and the archaecortex are the two primordial neocortical precursors that form the mammalian neocortex. In contrast to the arrangement in the planar cortex, six phylogenetically distinct “growth shells” are detected in the threedimensional thalamus and are designated after the corresponding schematic levels of Rolf Hassler’s paradigm of hexapartition of unit-thalamic inputs. The subthalamus and the epithalamus analogously represent the primordial diencephalic precursors of the mammalian dorsal thalamus, Both the neocortex and the dorsal thalamus evolved in response to the necessity for a more comprehensive blending of inputs from differing neuraxial levels. Unlike the age variable, the parameter of input specificity is most readily apparent in the dorsal thalamus; which is the site of termination for each major forebrain input. Accordingly, the fourteen individual units of the parameter of input specificity are designated after each of the specific input classifications projecting discretely to circumscribed thalamic sectors, An identical complement of input parameter levels also occurs in the cortex by way of thalamic relay across the internal capsule. Furthermore, each thalamic nucleus of specific parameter coordinates directs its main projection to cells of the cortex displaying identical coordinate values, establishing forebrain interconnectivity as an additional function of the dual parameter paradigm.
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