INPUT SPECIFICITY – EXTEROCEPTIVE, INTEROCEPTIVE, AND PROPRIOCEPTIVE (12,000 WORDS)© John E. LaMuth 2011
The exteroceptive class of forebrain inputs serves to keep the individual organism sensorily aware of the external environment. The major human exteroceptive senses are the visual, auditory, somesthetic, gustatory, vestibular, and olfactory modalities. Each modality projects to a specific region of the dorsal thalamus save olfaction, which projects directly to the paleocortex. Inputs to the thalamus are analyzed and relayed to precise areas of the cerebral cortex via the thalamic radiations. Each exteroceptive input evolves across the complete series of thalamic growth shells, projecting to a single nucleus within each growth shell. This organizational pattern is schematically illustrated in the master schematic grid as one vertical column within the format. Each series of thalamic nuclei within a given schematic column projects to the sequence of cortical age levels listed within the same unit-squares. In this manner, the input parameter relays to the neocortex without losing any of the specificity observed at the thalamic level. Each of the exteroceptive inputs is to be examined with regard to its specific differentiation across the sequence of growth shells and growth rings. The pattern of input organization that emerges serves as a precedent for specifying the interoceptive and proprioceptive inputs as well.
THE VISUAL SENSE
The visual modality is the sense most universally vital to the survival of the vertebrate line. Over the more restricted scale of primate evolution, the visual sense reaches its most dramatic stage of refinement within the human optic thalamus. The arboreal environment of tree-dwelling primates selectively enhanced advances in binocular vision and color sensitivity. This trend set the stage for the accelerated rate of expansion in the human visual system. The selective pressures for visual precision in the primal human endeavors of toolmaking and tracking initiated dramatic thalamic modifications over the relatively brief time course of human evolution. The rudimentary visual pulvinar nucleus of carnivores underwent so dramatic an expansion that it rates as the largest nucleus in the human thalamus. The posterior visual area of the human cerebral cortex is similarly amplified to the extent of forming a well-defined occipital lobe. The simultaneous addition of growth shells and growth rings during human evolution undoubtedly accounts for much of this rapid expansion.
The visual component of the most recent relay growth shell corresponds to the highly organized lateral geniculate nucleus. The human lateral geniculate nucleus is structured as a stack of six parallel cell laminae, numbered in an outward progression. Laminae 2, 3, & 5 receive object track fibers from the ipsilateral retina, whereas the contralateral eye projects to the remaining laminae 1, 4, & 6. Color vision also has been shown to exhibit a precise laminar specificity (De Valois, 1965). The partially analyzed visual input from this exquisitely organized nucleus is relayed via the Loop of Meyer and exclusively to the occipital lobe. The high degree of specificity for the primary visual cortex is so pronounced as to produce total blindness when damaged through trauma in humans.
For the visual system, the primary visual cortex is the striate area #17 receiving input from the lateral geniculate nucleus (LGN), respectively. The primary visual koniocortex is actually restricted to the prepolar portion of area #17, which represents both a cytoarchitectonic and myelographic differentiation maximum between the less developed oral and polar segments of area #17 (Sanides, 1966). The polar striate segment is functionally related to the central visual field, whereas the oral segment represents peripheral vision. The peripheral retina projects to the magnocellular LGN, whereas the macula projects to the parvocellular layers (Hassler, 1966). These facts appear consistent with the observations that the magnocellular LGN and the medial-posterior parvocellular LGN to the oral and polar prekoniocortical area #17, respectively, leaving the antero-lateral parvocellular LGN to project to the koniocortical prepolar area #17 (Juba, 1933).
The striate area #17 displays large pyramidal cells in lamina V denoting a medial ur-trend. The striate area #17 is concentrically surrounded by the visual portions of the next two older growth rings. The peristriate area #18 immediately circles the primary visual area, whereas the parastriate area #19 surrounds the aggregate of the two. The ventral complex of the pulvinar relays visual input to both of these phylogenetically older cortical areas. Nucleus pulvinar intergeniculatus of the first integrative level was cited by Hassler (1971) as receiving collaterals from the optic tract and projecting to area #18. Nucleus pulvinaris suprabrachialis of the second integrative level further relays visual input to area #19. The visual subthalamic ur-trend is further extended back in phylogenetic evolution as the crudely structured nucleus pulvinaris superficialis. This ancient subdivision of the pulvinar was cited by Yakovlev (1966) as a source of input for the visual area #36 of the proisocortical growth ring. Area #36 has been electro-physiologically demonstrated to correspond to a region mapped as the supplementary visual representation (MacLean, 1966). The subthalamic visual ur-trend is completed by a portion of the reticular nucleus that adjoins the lateral geniculate nucleus and receives collaterals from the optic tract. The reticular nucleus displays a distinct continuity with the visually-dominated pregeniculate nucleus of the primordial nonspecific age level. The pregeniculate nucleus was identified as a direct derivative of the subthalamus (Reinoso-Suarez, 1966), confirming the subthalamic origins of the entire visual sequence.
The subthalamus is not the only thalamic terminus for primordial visual inputs. As mentioned previously, the epithalamus of lower vertebrates represents the terminus for fibers issuing from the retina of the parietal eye. Ancient fossil remains of extinct species of jawless fishes clearly exhibit paired parietal eye-orbits symmetrically situated adjacent to the more well-defined lateral eye orbits. At one time in the distant past, the epithalamus undoubtedly received a dual optic projection that closely paralleled the main optic projection to the pregeniculate nucleus still in evidence today. The total atrophy of the parietal visual structures prior to the development of the later thalamic growth shells seemingly deprived the epithalamic ur-trend of sustaining inputs from the visual system. This sensory deficit appears to have been filled by collateral inputs from the optic tectum at subsequent stages of dorsal thalamic differentiation.
The optic tectum (or superior colliculus) occurs in the human species as a symmetrical pair of raised swellings on the posterior aspect of the midbrain. Fibers from the optic tract enter along the surface of the midbrain and proceed into the deeper laminae of the tectum. The optic tectum is the highest visual sensory center for the more primitive vertebrates that lack a well-developed thalamus. The visual tectum has, in fact, has been consider to be derived at the level of the diencephalon, only later to be displaced into the midbrain by subsequent growth pressures. “The optic tectum eventually formed the roof of the midbrain, but in lower vertebrates in which the cerebral aqueduct is not yet formed, the optic tectum simple extends over the midbrain as a laminated cortex, continuous at its rostral end with the diencephalon and separated from the underlying midbrain by extensions of the third ventricle, the optic ventricles.” (Sarnat and Netsky, 1974). The optic tectum loses much of its importance in higher vertebrates, the tecto-spinal tract being phased out in favor of visual relay rostrally to the newly developing thalamus.
Inputs from the optic tectum were initially incorporated into the very first if thalamic growth shell in the region of the nucleus limitans opticus. Limitans opticus is designated in reference to the local termination of collaterals from the brachium of the optic tectum (Hassler, 1959). Limitans opticus blends into the limitans medialis of the epithalamus, marking the beginning of the epithalamic ur-trend. This ur-trend continues through phylogeny as the massive medial division of the pulvinar nuclear complex. The medial pulvinar is an older thalamic region that spans two grow shells as the nucleus pulvinaris medialis dorsalis and nucleus pulvinaris medialis ventralis. The ventral segment of the medial pulvinar has been demonstrated to project to the proisocortical area #38 of the temporal lobe (Sequeira, 1973). The remaining portion of the medial pulvinar appears to continue this projection through the para-insular growth ring that spans the extent of the middle and inferior temporal gyri. The most recent two age levels of the tectal/epithalamic ur-trend correspond to the subdivisions of the massive lateral nucleus of the pulvinar. Nucleus pulvinaris lateralis superior projects to the base of the temporal lobe at a position left off by inputs from the medial pulvinar. Nucleus pulvinaris lateralis inferior of the most recent relay age level completes this cortical continuum by projecting to the middle parietal lobe near the posterior intraparietal sulcus. This sulcal region corresponds with the koniocortical visuo-auditory band shown to be derived along the lateral cortical ur-trend. The visuo-auditory band represents a myelographic maximum between areas #37 and #39. The accentuation of the outer pyramidal layer in the visual association regions, as well as a location of the visuo-auditory band lateral to the occipital continuation of the interparietal sulcus clearly suggests a developmental emphasis across the lateral ur-trend.
The lateral superior and lateral inferior pulvinar nuclei project to areas #37 and #39 respectively, with projections to the visuo-auditory band presumably emanating from the dense single fiber region at the boundary between these two nuclei. This most recent cortical age level is unusual in that the projections that it receives from lateral pulvinar are sparse in comparison to the lateral geniculate projection to area #17. The visuo-auditory band receives a wealth of inter-cortical fibers from striate area #17 suggested that this strip is modified into more of a visual association functions and in the human visual system. An analogous situation occurs that the thalamic level concerning the independence of inputs to the lateral pulvinar. The tectal projection to the lateral pulvinar is of tenuous proportions, undoubtedly due to the general reduction of the tectum relative to the direct visual projection to the lateral geniculate nucleus. The lateral pulvinar receives collaterals of the projections issuing from the lateral geniculate nucleus, indicating that the former is modified to function as the integrative association nucleus of the latter. This appears to be the only theory that explains the huge size expansion of the lateral pulvinar in the human thalamus.
The general pattern of organization that emerges to from this phylogenetic analysis of the visual sense is one of evolutionary conservatism compounded by functional modification. The epithalamic and subthalamic visual ur-trends are definitely represented in the human thalamus, although obscured at certain levels by the unavoidable atrophy of outmoded inputs such as the parietal eye. The corresponding lateral and medial ur-trends of the neocortex show a similarly prominent phylogenetic continuity in the occipital and temporal lobes. This general pattern serves as a fairly accurate model for the inclusion of auditory inputs into the forebrain, now to be described.
THE AUDITORY SENSE
The auditory sense, represented adjacent to the visual areas in the human cortex, evolved much later in evolution than the other exteroceptive senses. Airborne detection of sound did not become a selective survival factor until roughly 400 million years ago, when the first air-breathers crawled out from the water into a terrestrial environment. The low-postured ancestral amphibians and reptiles capitalize chiefly upon the vibrational signals transmitted through their ground support. The sound-detecting cranial ear first came into its present form at the mammalian stage of vertebrate evolution. The mammalian cochlea evolved as a modification of the vestibular semicircular canal system. Primary sensory fibers issuing from the cochlea usurped the preexisting pathways to the brainstem, terminating in the modified dorsal and ventral cochlear nuclei. This input modification of the brainstem is paralleled by changes in the ascending pathways leading to the forebrain. The mainstream auditory pathway leading to the inferior colliculus widely varies in the number of synaptic interruptions, making a precise schematic pattern of the staggered circuitry much more difficult to follow than the phase-specific synapse pattern seen for the visual system. The inferior colliculus appears as a prominent swelling in the region of the midbrain that serves as the major auditory center for lower vertebrates. In higher mammals, the inferior colliculus serve a more minor role, relaying auditory inputs the nucleus geniculatus medialis of the dorsal thalamus.
The medial geniculate nucleus in man is composed of a number of subdivisions that span the entire sequence of thalamic growth shells. The major relayed subdivision of the medial geniculate nucleus corresponds to the nucleus geniculatus medialis fibrosus, designated in reference to its thick felt-work of individual fibers. This highly organized subdivision, nevertheless, lax law laminated organization previously shown for the lateral geniculate nucleus, indicating the more diffuse character of the ascending auditory pathway. Geniculatus medialis fibrosus projects to auditory areas #41 and #42 of the koniocortical growth core. This dual auditory projection of geniculatus medialis fibrosus suggests a lack of tonotopic specificity at the level of the thalamus. Electro-physiological investigations on the rhesus monkey employing a musical tone scale, however, have indicated a distinct topographical specificity at the level of the neocortex. Higher tones are represented in the medially situated area #41, whereas deeper tones are associated with the lateral area #42. These results are foreshadowed at the initial stages of the auditory tract, where the dorsal cochlear nucleus is specific to the treble end of the cochlea, whereas the ventral cochlear nucleus is concerned with the base scale of the cochlea. It would appear that the tonotopic specificity of the cochlear nuclei is preserved all the way through to the cortical level, although not always readily apparent at the intervening levels.
Lesion studies within the primary koniocortical area #41 have been demonstrated to exhibit retrograde degener¬ation in the posterior medial geniculate (Hassler’s medialis geniculatus fasciculosus). The other pleurokonio- belt is represented by the more postero-lateral #22, which is intermediate between the koniocortex and the temporal pole, rather than the insula. That the superior temporal gyrus is one projection zone of the oral pulvinar suggests that the subnucleus, pulvinaris oro-ventralis, which is situated adjacent to the medial geniculate, provides the thalarnic input to this latter pleurokonio-belt.
The remaining koniocortical area #42 has been conclusive1y cited as receiving input from the newer portions of the medial geniculate. In the rhesus monkey, area #42 demonstrates immediate proximity to belt area #7 (Fpt) while in man, #42 appears to be drawn ventrally away from the interparietal sulcus, whereby retaining its intimate continuity with area #41. This migration of area #42 to a location surrounded by the pieurokonio-area #40, demonstrates the growth pressure plasticity of the boundaries that actually delimit successive cortical growth rings. The thalamic projection to the pleurokonio- areas surrounding #42 is presumably analogous to that shown in the case of #41. However, the nucleus pulvinaris oro-lateralis, rather than ventralis, apparently projects to the prekonio-area # 7 of the posterior parietal lobe. These observations are in agreement with Hasslers designation of geniculatus medialis fasciculosus and pulvinaris oralis as the integrative nuclei related to auditory input.
Auditory input represents a prime example of an extrinsic exteroceptive thalamic input. In studies of the cat, all auditory input to the medial geniculate is relayed through the inferior colliculus of the mid¬brain (Van de Groot 1967). The overlapping array of nuclei and fiber tracts along the auditory pathway, complicates recognition of a distinct pair of components analogous to those shown for visual input. Area #42 displays conspicuously large pyramidal cells in lamina IIIc denoting a lateral corticoid trend of differentiation. Area #41 demonstrates a greater size emphasis on the internal pyramidal layer, implying a corresponding developmental emphasis from the medial ur-trend.
The next oldest age level within the medial geniculate nucleus corresponds to the nucleus geniculatus medialis fasciculosus. This nucleus is delineated from the geniculatus medialis fibrosus through the appearance of numerous fascicles of nerve fibers for which it is named. Geniculatus medialis fasciculosus projects to the cortical area that laterally borders area #42, corresponding to the prekoniocortical area #40. This lateral cortical ur-trend is further continued by area #52 of the supra-temporal plane of the temporal lobe. Area #52 is the auditory constituent of the parainsular growth ring identified through electro-physiological techniques as the supplementary auditory cortex. A portion of the adjoining insular area #13 also has been shown to receive auditory input in a related study (MacLean, 1966). Both of these cortical areas have been shown to receive projections from the nucleus geniculatus medialis magnocellularis. Geniculatus medialis magnocellularis is regarded as a more ancient subdivision of the medial geniculate nucleus, a distinguished by its conspicuously larger type of nerve cell. Hassler (1959) assigned this nucleus to his composite-multisensory division in accordance with its documented tactile inputs. Further investigations have demonstrated a similar overlap of auditory and tactile inputs in the portion of the insular cortex that receives the projection from this nucleus. The completion of the auditory growth shell sequence invokes the nucleus geniculatus medialis limitans of the reticulate feedback age level. As mentioned previously, the nucleus limitans approaches into continuity with the habenula, wherein rounding out this portion of the epithalamic ur-trend dealing with auditory sense.
In addition to the foregoing account, the medial geniculate appears to have been differentiated along a subthalamic ur-trend as well. The newer growth shells of the medial geniculate nucleus come into approximation with the oral (anterior) if he portion of the pulvinar nucleus. Hassler (1971) identified the oral pulvinar as the second integrative nucleus of the auditory input classification. In re-evaluation, however, the massive oral pulvinar appears to span several growth shells of the subthalamic ur-trend. Nucleus pulvinaris oroventralis, by reason of close proximity to the medial geniculate, corresponds to the auditory representation of the first intergrative level. The more poorly differentiated pulvinaris orolateralis is assigned to the auditory ur-trend portion of the second integrative growth shell. The remaining sub-nucleus pulvinaris oromedialis extends the auditory ur-trend one age level further into the composite-multisensory classification. This sequence of nuclei in the oral pulvinar project (in the given order) to the corresponding series of cortical age levels spanning the medial ur-trend of the superior temporal gyrus. Auditory area #22 extends from the pole of the temporal lobe into continuity with koniocortical area #41. Von Economo subdivided his equivalent of Brodmann’s area #22 into subareas TA-1 and TA-2, which coincide with the paralimbic and prekoniocortical age levels of the superior temporal gyrus. The sequence is completed by the limbic area #38 (TGD), which caps the temporal pole on its dorsal aspect. All three of these temporal lobe areas show indications of a primitive type of sensory auditory function during electro-cortical recording (Sanides, 1973). The subthalamic ur-trend extends medially around the temporal lobe in the guise of the elongated peri-limbic area #35. Area #35 enters into continuity with the archaecortex, wherein rounding out the medial auditory ur-trend.
The forebrain representation of the auditory sense has been shown to display many points in a caller with the previously discussed visual sense. The auditory relay area of the dorsal thalamus also evolved across both dorsal and ventral ur-trends analogous to the arrangement in the more posterior visual thalamus. The koniocortical areas of the auditory cortex differentiated by way of both the medial and lateral neocortical ur-trends consistent with the dual arrangement previously established for the visually dominated occipital lobe. The remaining exteroceptive sense of touch does not vary appreciable from preestablished pattern. The tactile sense shows an evolutionary pattern in the human forebrain that spans a similar set pattern of constituent ur-trends.
THE TACTILE SENSE
The exteroceptive sense of touch differs from the long-range senses of sight and sound in that all tactile signals impinge directly upon the periphery of the organism. The tactile sense serves to convey a sense of awareness of physical changes within the environment (touch) or mechanical damage to the organism (pain). The simple yet vital functions have preserved the tactile sense as a universal feature of vertebrate evolution. The representative ancestral chordate Amphioxus demonstrates a well developed somatosensory system in the complete absence of any other organs of special sense. As might be surmised, the forebrain of Amphioxus is only incipiently represented, the tactile sense functioning chiefly through the intrinsic segmental circuitry of the spinal cord and brain stem. Somatosensory inputs gradually became relayed to the more rostral levels of the central nervous system prompted by the encephalization of the forebrain. This trend reaches its culmination at the mammalian stage of development with the establishment of the direct spinothalamic tract to the forbrain.
The spinothalamic tract in humans conveys the sense of temperature, pain, pressure, and a general contact sense. The sensory aspects are mediated by the nonspecific fine nerve endings in the skin which connect with the cell bodies within the dorsal root ganglia of the spinal cord. These secondary neurons, in turn, send axons to the opposite side of the spinal cord where they ascend in the outlying white matter to reach the thalamus. Other specific receptors in the skin relay tactile sensibility to the thalamus through the prominent dorsal column spinal tract. Meissner’s corpuscles and comparable hair follicle structures in the superficial skin layer, as well as the deeper lying Pacinian corpuscles, mediate the finer senses of a light touch and pressure. The cell bodies associated with these skin receptors are also located within the dorsal root ganglia similar to the arrangement for the spinothalamic tract. The axons from these primary neurons enter through the dorsal spinal root and give off direct collaterals that ascend in the cuneate and gracile spinal tracts third to synapse upon the secondary neurons of the nucleus cuneatus and gracilis. Tactile sensibility from the upper extremities terminates in the nucleus cuneatus, whereas the lower extremities relay to the nucleus gracilis. The secondary sensory projections from these brainstem nuclei cross to the opposite side of the medulla and ascend in the medial lemniscus to reach the somatosensory portion of the thalamus.
Tactile sensibility from the face and head region alternately relays to the thalamus through the fifth cranial nerve of the human brain stem. Cranial sensations of pain, temperature, and touch are initially transmitted by primary receptor cells with cell bodies in the trigeminal (Gasserian) ganglion. The trigeminal nerve enters the brainstem to synapse in the chief sensory trigeminal nucleus. Secondary fibers decussate upon exiting the chief trigeminal the nucleus and join the medial lemniscus in transit to the thalamus. This component mediates the sense of touch and is homologous to the cuneate and gracile spinal tracts. The trigeminal nerve also terminates in the descending trigeminal nucleus of the brainstem, which mediates the sensations of pain and temperature. The secondary fibers from this trigeminal component also travel within the medial lemniscus and are considered to be the cranial analog of the direct spinothalamic tract.
The dorsal thalamic region receiving the class of somatosensory inputs corresponds to the caudal subdivision of the lateral thalamic complex. This lateral complex represents the largest mass of nuclei within the dorsal thalamus spanning virtually its entire length with respect to its lateral aspect. The lateral complex blends caudally with the pulvinar complex, and on its medial aspect borders the massive and (and as yet to be described) medial thalamic group. The lateral thalamic mass has been variously subdivided according to fundamental German and English traditional nomenclatures. The German nomenclature introduced by Vogt (1941) has been modified by Hassler (1959) to offer a highly precise and comprehensive overview of the lateral thalamic region. According to Hassler’s scheme, the lateral mass is partitioned into four basic longitudinal segments corresponding to a sequence of caudal, intermediate, oral (anterior), and polar segments. The three segments situated rostrally to the caudal subdivision are concerned with proprioceptive inputs, and their discussion will be reserved until this corresponding section. It should be mentioned in passing, however, that all four subdivisions are further subdivided from top to bottom into ventrolateral, zentrolateral, and dorsolateral subdivisions. The ventrolateral layer is the most structurally developed set of nuclei and corresponds to the most recent relay growth core of the thalamus. The zentrolateral and dorsolateral layers are alternately identified as constituents of the first and second integrative age levels, respectively.
Spinothalamic input to the lateral complex spans all three age levels in the caudal subdivision. The primary thalamic relay nucleus corresponds to nucleus ventro-caudalis posterior, situated at the caudal pole of the lateral mass ad¬jacent to the oral pulvinar. In line with the rostro-caudal continuity so far cited, ventro-caudalis projects to the most recently evolved portion of the parietal lobe, the well myelinated visuo-sensory band of the koniocortical growth core. Furthermore, in addition to the visuo-sensory band, the primary tactile area #3b also receives input from nucleus ventrocaudalis. The classical koniocortical strip #3b is flanked by the prekonlo¬cortical area #2 intermediate to the insula) and area #1, which demonstrates close affiliation to the dorsal hemisphere margin (Hassler 1966). Similar to the configuration in the cortex, the nucleus ventrocaudalis parvocellularis, which projects to area #2, blends into nucleus ventrocaudalis from below, while the nucleus zentrocaudalis, which supplies input to area #1, grades into ventrocaudalis from above. The koniocortical visuo-sensory band represents an amyelographic maximum between parietal areas # 7 and #40. It would appear that the somatosensory and auditory realms share a common set of associational prekoniocortices in the parietal region. MacLean 1971) demonstrated an even more extensive overlap of somatosensory and auditory modalities in the more ancient insular cortex of primates. This sensory overlap is not inconsistent in light of the common functional origin of audition and somesthesia. The auditory nerve phylogenetically evolved as the fusion of specific sensory components of several of the branchial nerves (Sarnat & Netsky 1974). The branchial nerves are homologous in form and function with the spinal nerves of the somatosensory system. Hence, differentiation of the association regions of these two modalities was not heterogeneous enough to promote a clear-cut areal separation of von Economos’ subdivision of area #7 into anterior (Pem) and posterior (Pep) segments tends to suggest some specialization is inherent even in such a diffusely patterned association area. The projections of the somatosensory association nuclei should display only negligible overlap with the auditory projections from the oral pulvinar. Nucleus ventrocaudalis posterior is the topographical candidate for projection to the visuo-sensory band. The association prekonio-relay nuclei are presumed to be the caudal segments of those nuclei shown for the case of # 3b.
Somatosensory imput is another example of an exteroceptive component of the class of extrinsic thalamic inputs. The cortical projection areas # 3b and the visuo-sensory band exhibit an intrinsic functional specificity of input. Area #3b is the koniocortical represent¬ation concerned with epicritic tactile sensibility, transmitted by spinal dorsal columns. Large pyramidal cells in lamina IIIc of #3 imply a direct developmental emphasis from the lateral corticoid trend. The visuo-sensory band, on the other hand, is located dorsal to the interparietal sulcus. Location of this band, medial to the ur-trend limiting sulcus denotes a strict developmental accentuation on the medial corticoid trend. Demonstration of a somatic pain representation in the posterior parietal lobe suggests that the somatosensory association region is mainly concerned with nociceptive tactile sensibility. This observation is in accordance with spinothalamic tract projection to the posterior portion of the ventrocaudal nucleus.
The first integrative age level of the spinothalamic ur-trend coincides with the dorsally situated zentro-caudalis posterior. Zentro-caudalis posterior receives the collaterals of spinothalamic input and relays to parietal associa¬tion area #7. The gradient within the lateral complex is continued by nu¬cleus dorso-caudalis, which according to Hassler, appears as modestly sized nucleus situated in a plane above the posterior part of ventrocaudalis. Dor¬so-caudalis relays collaterals of spinothalamic input to the primitive area #31 of themedial aspect of the pariental lobe.
The prominant termination of spinothalamic fibers in the posterior part of ventro-caudalis is the general consensus for many researchers (Scheibel & Scheibel, 1966). Although this finding is in variance to the scheme proposed by Hassler, the criteria upon which this modification is based are borne out in the general context of the dual parameter grid. Pain information communicated through the spinothalamic tract is relayed throughout the parietal lobe after integrative processnd in the caudal thalamus. This cortical projection is consistent with electrophysiological findings, which point to the presence of a diffusely organized pain representation in the lateral parietal lobe.
The remaining two age levels of the spinothalamic ur-trend correspond to the nucleus dorsalis superficialis and the nucleus reticulatus caudalis of the posterior thalamus. Nucleus dorsalis superficialis is situated as the anterior continuation of nucleus pulvinaris superficialis (in the dorsomedial margin of the thalamus). Nucleus dorsalis superficialis was classified as one of the limbic nuclei by Yakolev (1966), who cited projections to the limbic area #23 of the proisocortical age level. Nucleus reticulatus caudalis represents the earliest growth shell segment to receive spinothalamic collaterals. This nucleus is presumed to project to the ancient retrosplenial cortex on the medial aspect of the human cerebral hemisphere. The remaining anterior portion of lateralis caudalis exhibits a quite different type of somesthetic specificity. Nucleus ventro-caudalis anterior is further subdivided along a medio-lateral plane into internal and external segments. Controlled lesion studies in primates have demonstrated that the external segment is specific to somatosensory input from the nucleus cuneatus and gracilis, whereas the internal segment is specific to terminals from the main trigeminal nucleus. The medial-most portion of the internal segment mediating sensations from the oral cavity coincides with the relayed area for the taste sense. Hassler also describes the termination of the cervicothalamic tract represent-ing hair-bending sensation in ventro-caudalis anterior. N. ventro-caudalis anterior relays all of these sensory components to the classical somatosensory area #36 of the post-central gyrus. According to electrophysiological findings, area #36 extends the longitudinal extent of the gyrus in a somatotopic pattern ordering the leg-trunk-arm-head-tongue/taste representations into a media lateral hemisphere gradient.
Immediately subjacent to nucleus ventrocaudalis anterior lies nucleus ventro¬caudalis parvocellularis, designated for its characteristically smaller sized nerve cells. This nucleus of the first integrative level is similarly sub¬divided into internal and external segments specific to the head/body dicho¬tomy. This parvocellular subdivision projects to the area #1 association region adjacent to the koniocortical area #36. Using the single cell recording tech¬niques in monkeys, Montcastle (1964) showed that sensory thresholds for cells in ventrocaudalis parvocellularis were higher than in the adjacent relay sub¬division. This thalamic age difference coincides to the lower specificity and higher threshold characteristics of area #1 relative to area #36.
The age gradient is extended one level further under the guise of nucleus ventro-caudalis portae. This poorly organized nucleus occupies the ventral-most level of the ventrocaudal thalamic complex. In line with continuity con¬siderations, this nucleus projects to the parainsular area #43 that coincides with the secondary somatosensory representation. The oldest pair of growth shells and growth rings for this somatosensory ur-trend parallels the pattern cited for the corresponding segment of the auditory ur-trend. The multimodal character of these most ancient age levels is consistent with the closely related origins of both the somatosensory and auditory inputs.
The rostral-most extension of the somatosensory representation concludes this discussion of the exteroceptive class of forebrain inputs. The three main categories of visual, auditory, and tactile input were each demonstrated to span both epithalamic and subthalamic ur-trends through the course of human forebrain evolution. This parameter of input specificity, in turn, is preserved at the neocortical level by way of preferential projections from the corresponding growth shell gradients to the medial and lateral cortical growth rings. These medial and lateral ur-trends, furthermore, exhibit a strict unit of alternation in relation to one another across the entire rostro-caudal extent of the posterior neocortex. This orderly pattern proves to be the rule rather than the exception for the adjacent proprioceptive region of the human forebrain, as well.
THE PROPRIOCEPTIVE CLASS OF INPUTS
The class of proprioceptive input differs from the exteroceptive type in that the sensations arise from of the inpetus of the body's own spatial orientation. This proprioceptive category encompasses the sense of balance (vestibular input), the sense of position (limb and joint afferents), and the sense of movement (muscle sensations). Each variety of primary proprioceptive afferents ascends to a rostral motor center for subsequent relay to the thalamus. These motor nuclei are classified into either brainstem or diencephalic functional systems. Motor ganglia that derive their origin from the diencephalic segmental level represent the class of proprioceptive inputs that are intrinsic to the forebrain. In contrast, the collection of motor nuclei indigenous to the subforebrain neuraxial levels are termed the class of extrinsic proprioceptive inputs.
The extrinsic category of proprioceptive inputs encompasses the cerebellar-vestibular complex of the pons and medulla. The cerebellum is a massive cortical structure overlying the dorsal aspect of the brainstem. Although the cerebellum is considerably smaller than the cerebrum, its total cortical surface area approaches that of the neocortex due to a more extensive gyral folding pattern that imparts an almost corrugated appearance. Despite its commanding size, the cerebellum does not appear to be the initiator of movement, rather functions in collusion with the vestibular system in the maintenance of equilibrium and muscle tone. The cerebellum does not appear to play a major role in the conscious appreciation of intellectual or perceptual sensibility, relegated to only an accessory role in the context of the mind brain interaction. Conscious enactment of the precise motor skills initiated by the cerebral cortex, however, depends to some degree upon the extensive reciprocal connectivity between the cerebrum and the cerebellum.
The cerebellum functions to synchronize the timid between muscles as a whole, or within a group, whether the action is at an automatic or conscious level. Patients with cerebellar lesions are capable of executing the general outlines of a complex movement, although it appears disjointed for reason of the lack of finer muscular coordination. The cerebellum smoothes out the performance of muscle groups by delicately regulating muscular tension in such diverse activities as standing, running, or playing the piano, etc. The cerebellum functions similar to a servomechanism in a negative feedback system, acting to prevent tremor during motion and, accordingly, maintaining stability during movement. The output from the cerebellum cortex passes exclusively to the deep cerebellar nuclei embedded within the surrounding white matter, as well as to the vestibular nuclei of the medulla. It is this series of secondary nuclei that relay the proprioceptive input from the cerebellar cortex to the thalamus.
The proprioceptive center of the human forebrain is situated immediately anterior to the exteroceptive regions of the cerebral cortex and the thalamus. The intermediate segment of the lateral thalamic complex is situated just rostral to the somatosensory caudal sector. The nucleus lateralis intermedius receives its input from the vestibular complex of brainstem motor nuclei. The primary relay nucleus for the intermediate segment corresponds to the well differentiated nucleus ventro-intermedius. This nucleus is further subdivided into the external and internal segments reminiscent of the similar arrangement within the nucleus ventro-caudalis. Nucleus ventro-intermedius internus has been cited by Hassler (1971) as the chief site of termination for input from the lateral vestibular nucleus. Proprioceptive signals from the semicircular canals of the inner ear are relayed to the vestibular complex of the medulla. The lateral vestibular nucleus is the motor component of the vestibular complex that gives rise to the efferent vestibulo-spinal tract. Other nuclei of the vestibular complex do not give rise to spinal tracts but rather take on a sensory character. These areas are the source for the reported ascending vestibular projection that parallel the auditory projection to the temporal lobe. The vestibular motor emphasis on head orientation via the neck musculature is consistent with its internal representation within the nucleus ventro-intermedius. The external segment of the ventro-intermedius has been demonstrated through electro physiological studies to receive Ia spindle fiber afferents ascending within the dorsal spinocerebellar tract (Anderson, Landgren, and Wolsk, 1966). A portion of the cerebellar tract is diverted from its destination in the cerebellar cortex to relay within the nucleus cuneatus externus of the medulla. The ascending projection from this relay nucleus parallels the somatosensory pathways of the medial lemniscus for termination in the nucleus ventro-intermedius externus.
The primary motor and premotor regions of the neocortex supplant the sensory areas in regions anterior to postcentral gyrus. Although these regions are characteristically agranular to disgranular, the several indigenous heterotypical maximums are regarded as elements of the highly differentiated koniocortica! core of development. The two motor koniocortical areas are #4γ and 3a that receive input from nucleus ventro-oralis posterior and nucleus ventro-intermedius, respectively. The nucleus ventro-oralis posterior and adjacent portions of ventro-oralis internus have been demonstrated to relay impulses from the parvocellular cerebellar dentate nucleus to the classical motor area gigantopyramidalis (#4γ). Prekonio- area #4α, which lacks giant pyramidal cells, broadens ventrally of area #4γ, while a similarly deficient area #4s widens on the dorsal anterior margin of area #4γ. Analogous to the arrangement in the cortex, the nucleus ventro-oralis medialis blends into the nucleus ventro-oralis posterior ventro-medially, whereas the nucleus zentro-oralis grades over into the latter nucleus dorsally. These corresponding continuity suggest that the zentro-oral nucleus projects to area #4, whereas the nucleus ventro-oralis medialis projects to area #4α.
The association region of the motor areas is represented by the band-like area #3a located on the posterior wall of the central sulcus and possessing giant pyramidal cells, as well as a distinct inner granular layer. The fundic subdivision of area #3a (PA-1) processing a broadly and radiately striated lamina III appears to represent the koniocortical maximum of the area #3a region. The nucleus ventro-intermedius has been demonstrated to be the specific relay nucleus to area #3. Following the proximity analogy mentioned in the case of area #4γ, the nucleus zentro-intermedius should be expected to project to the prekonio- region of area #3a (PA2). The nucleus ventro-intermedius internus has been demonstrated by Hassler to receive input from the vestibular complex. Vestibular motor emphasis on head orientation via the neck musculature is consistent with the internal vestibular representation in nucleus ventro-intermedius. Vestibular inclusion into the cerebellar classification is substantiated in reference to direct projections from the cerebellar cortex to the vestibular, as well as to the deep cerebellar nuclei (Sarnat and Netsky, 1974).
Ia spindle fiber afferents of the dorsal column tract were electrophysiologically demonstrated to terminate in the nucleus ventro-intermedius externus (Anderson, Landgren, & Wolsk 1966). Similar Ia afferents to the anterior lobe of the cerebellum via the dorsal spinocerebellar tract substantiate the motor functional character of nucleus ventro-intermedius. Electrical potentials in ventro-intermedius evoked during dorsal column stimulation, might also result from stimulus relay around the cerebellar cortex-interpositus pathway. Either interpretation is consistent, however, with the concept of representation of input from the body in the external segment of the ventral nuclei.
The vestibular and deep cerebellar nuclei, therefore, represent the motor component of the class of extrinsic thalemic inputs. The various nuclei comprising this input category are all functional constituents of the brainstem cerebellar complex. The corresponding cortical projection field is clearly composed of granular and agranular components corresponding to #3a and #4γ, respectively. Determination of the accentuated ur-trend for either of these regions is unattainable due to invalidity of the corresponding criteria. The distended deformation of the motor regions into an orientation parallel to the coronal sulcus nullifies any correlation with the axial ur-trend limiting sulcus. In addition, each motor region displays large pyramidal cells in both internal and external pyramidal cell layers. For area #4, the pyramidal cells of lamina V appear to have been incidentally magnified in size to sustain the lengthy axons of the cortico-spinal tract. In relation to the alternating ur-trend pattern shown for the other cortical regions, area #4γ displays a lateral ur-trend, while area 3a demonstrates a medial ur-trend.
In summary review, both the ventro-intermedius externus and internus project to the strip area #3a (area PA of von Economo) located on the posterior wall of the central sulcus. The fundic subdivision of the area #3a (PA-1) exhibiting a radiately striated lamina III corresponds to the koniocortical maximum, in contrast to the more typical adjoining subdivision (PA-2). Nucleus zentro-intermedius of the first integrative growth shell protects to the prekoniocortical (PA-2) subdivision of area #3a. Similarly, nucleus dorso-intermedius of the second integrative growth shell continues this ur-trend continuity by projecting to paralimbic area #5 that is situated upon the more anciental one aspect of the hemisphere. Both zentro-intermedius and dorso-intermedius are split into internal and external subdivisions that respectively parallel the vestibular/spindle fiber specificity previously established for nucleus ventro-intermedius. Nucleus ventro-intermedius also exhibits an additional dorsal subdivision, the nucleus ventro-intermedius superior. This rudimentary nucleus indicative of the composite multisensory growth shell relays to the ancient limbic area #24 of the cingulate gyrus. The subthalamic ur-trend reaches its furthest extension as the intermediate subdivision of the nucleus reticulatus, with which relays to the most ancient age level of the limbic hemisphere.
The oral segment of the lateral thalamic mass is similarly concerned with proprioceptive input. Nucleus ventro-oralis corresponds to the primary relay age level for the remaining classes of proprioceptive inputs. Ventro-oralis externus is subdivided into rostral and caudal segments identified as ventro-oralis anterior and ventro-oralis posterior. It is the posterior subdivision of ventro-oralis that is concerned with the remaining class of cerebellar extrinsic inputs. Both nucleus ventro-oralis posterior and the adjacent portion of the nucleus ventro-oralis internus correspond to primary terminus for inputs from the dentate cerebellar nucleus. The well differentiated dentate nucleus, in turn, relays the input from the lateral regions of the cerebellar cortex. The cerebellar cortex is the main projection field for both the spinocerebellar (body) and the trigemino-cerebellar (cranium) tracts. This observation corroborates the pattern of dual dentate projection to both internal and external segments of ventro-oralis.
The classical motor area #4γ evolved over a medial ur-trend gradiant characterized by an expanding prominence of lamina V pyramidal cells if over the phylogenetic time scale. Krieg (1959) working with the rhesus monkey demonstrated that the medial extension of the regio gygantopyramidalis ends very abruptly in region of generalized stratification that more closely resembles the adjoining premotor area #6. The additional preponderance of giant pyramidal cells in lamina III of area #4γ suggests that the classical motor area is actually derived across a lateral ur-trend gradient that spans the bulk of the precentral gyrus on the hemisphere convexity. The less specialized aspect of area #4 (#4α) corresponds to the prekoniocortical age level that predates the area #4γ koniocortex proper.
In terms of the thalamus, the cerebellar segment of the epithalamic ur-trend is continued into the more ancient age levels by way of the nucleus ventro-oralis medialis. The nucleus ventro-oralis medialis extends from the ventro-oral segment as a distended tongue of cells that stretches into a rostro-medial continuity with the very oldest thalamic age levels. Hassler (1959) describes an abrupt change in cell size and fiber structure occurring immediately within ventro-oralis medialis, suggesting that this nucleus actually spans a pair of growth shell segments. This observation is consistent with its proposed projection to areas #50 and #14 of the anterior insular cortex. The cerebellar epithalamic ur-trend reaches its furthest extension under the guise of the nucleus lateropolaris magnocellularis, respectively designated for its large type of multi-polar nerve cells. Hassler cites the occurrence of dentate input terminals entering nucleus lateropolaris magnocellularis for relay to the more ancient portions of the insular cortex. This nucleus represents the motor component of the composite multisensory age level, confirmed by the prominent inclusion of additional types of motor input. This related functional aspect of lateropolaris magnocellularis will subsequently be described in the following discussion relating to the intrinsic class of forebrain proprioceptive input.
THE INTRINSIC CLASS OF PROPRIOCEPTIVE INPUTS
The intrinsic class of thalamic motor nuclei correspond, for the most part, to the extra-pyramidal motor system. This term was coined in reference to the functional autonomy of this system relative to the more prominent cortico-spinal tract projecting from the cells of the motor cortex to the pontine cerebellar nuclei and the motor neurons of the spinal cord. This extra-pyramidal motor subdivision includes such nuclei as the globus pallidus and the subthalamic nucleus of Luysii. Contrary to their intrinsic thalamic classification, these two nuclei are imbedded within the white matter of the telencephalon rather than the diencephalon. Embryological studies by Reinoso-Suarez (1966), however, have demonstrated that the globus pallidus and the subthalamus are derived from the diencephalic neuraxial level, being rostrally displaced across the forebrain dividing line by evolutionary growth pressures. The globus pallidus has been implicated in the motor disturbance syndrome of Parkinson's disease in cases where this nucleus is selectively damaged by carbon monoxide poisoning. Lesions of the subthalamic nucleus have similarly been implicated in the severe tremor syndrome of hemiballism.
Also included within the intrinsic classification are the direction-specific motor nuclei of the diencephalon. These were extensively studied for over two decades by W. R. Hess (1940) employing a series of over 400 cats. The electrical stimulation of the feline forebrain resulted in a number of distinct patterns of behavior I observed while in an unrestrained postural state. The raising, sinking, turning, and rotary movements elicited through the implanted electrodes were ascribed to localized diencephalic structures using histological techniques. By introducing small electrolytic lesions through the same electrode, the presence of ascending projections to the lateral thalamic complex were commonly observed. The thalamic relay of these direction-specific inputs to the motor regions of the cortex predicts a similar repertoire of motor phenomena associated with the electro-cortical stimulation of corresponding areas. Employing a slightly modified cortical technique in cats, Hassler (1966) demonstrated a complete complement of behavioral effects matching the pattern of localization that would be predicted based upon the criterion of thalamo-cortical connectivity. A mixed pattern of response was sometimes elicited by stimulating a singular locus in the diencephalon. Rotary and raising movements of the head were most often associated with simultaneous contraversive turning movements of the body. These observations suggest that the selective reflects movements represent different functional aspects of the same motor system. These speculations are further confirmed when the results were applied to the human forebrain by Hassler in his 1971 hexapartition treatise.
The rostral-most portion of the lateral thalamic complex represents the thalamic terminus for the intrinsic class of motor inputs. The anterior portion of the nucleus ventro-oralis receives the relay age level projection from the internal segment of the globus pallidus. The total body (contraversive) movement pattern elicited during electro-stimulation of the globus pallidus, in addition to its external representationhe nucleus ventro-oralis suggest that this motor component mediates proprioceptive sensibility relating to the trunk and the extremities. The immediately adjacent portion of nucleus ventro-oralis internus represents the termination site for ascending input from by interstitial nucleus of Cajal. In addition to its ascending projection, the interstitial nucleus also gives rise to the descending interstitio-spinal motor tract. This nucleus also gives rise to a bilateral projection to the oculomotor and trochlear midbrain that control the eye musculature. The rotary head movements evoked through stimulation of the interstitial nucleus (Hassler, 1966) together with its internal projection to the ventro-oral nucleus, suggests a motor function relating to the head region. Interconnections between the interstitial nucleus and the internal globus pallidus indicate that these two nuclei represent different functional aspects of a common motor group.
Both the nucleus ventro-oralis anterior and the adjacent nucleus ventro-oralis internus project to area #6aα of the koniocortical age level. The overlying nucleus zentro-oralis similarly relays to the adjoining area #6aβ. This topographical continuity is continued by nucleus dorso-oralis, which projects to the more ancient portion of area #6 that is situated on the inaccessible medial aspect of the hemisphere. In his 1959 parcellation treatise, Hassler does not make mention of an internal/external split in nucleus zentro-oralis. The correspondingly proposed subdivisions of nucleus dorso-oralis appear somewhat artificial in this regard, indicating that the internal and external segments are each indigenous to separate thalamic growth shells. This subthalamic ur-trend finally terminates in the vicinity of the nucleus reticulatus oralis, which projects to the most ancient retrosplenial portion of the cingulate gyrus.
The remaining motor components of the intrinsic class of proprioceptive inputs project to the rostral-most pole of the lateral thalamic mass. This thalamic region was identified as nucleus ventro-anterior by English writers, but was retermed nucleus lateropolaris by Hassler to avoid confusion with the neighboring antero-ventral nucleus. The lateropolar complex fits like a cap over the rostral pole of the lateral thalamic mass, effectively obscuring the trilaminar composition characterizing the other segments. According to various criteria, Hassler assigns the nucleus lateropolaris externus and internus to his primary relay age level. The external lateropolar segment was cited by Hassler to receive relay input from the external portion of the globus pallidus. Both the external and internal segments of the globus pallidus elicit twisting movements to the side of the body contralateral to the hemisphere of the brain that is being stimulated. The internal lateropolar nucleus was cited as the terminus for a non-pallidar type of input presumably related to the interstitial classification (Hassler, 1959). Interconnections linking the praestitial nucleus and the external globus pallidus suggest that these two subdivisions function as a common motor unit. Electrical stimulation of the praestitial nucleus elicits raising movements of the head consistent with its proposed projection to the internal segment of lateropolaris.
Both subdivisions of the nucleus lateropolaris project to the premotor koniocortex of the inferior frontal gyrus corresponding to area #44. The older portion of area #44 not displacing giant lamina IIIc pyramidal cells represents the cor-responding termination site for inputs issuing from the adjoining nucleus lateropolarjs basialis. This topographical pattern is continued into the next older age level as the projection from the rudimentary nucleus lateropolaris superior to the similarly developed, parainsular area #50. The dorsal motor ur-trend reaches its furthest extension under the guise of nucleus latero-polaris magnocellularis of the composite multisensory age level. N. lateropolaris magnocellularis was additionally cited as receiving cerebellar projections consistent with its multi-sensory classification Postmortem brain autopsies indicate a projection from N. lateropolaris magnoceflularis to areas #44 and #16 the ancient insular lobe. This completed description of the lateral thalamic complex rounds out the analysis of the class of proprioceptive thalaniic inputs. The intrinsic and extrinsic categories of proprioceptive input each project to a dorsal/ventral set-pairs of ur-trends within the lateral complex. These complementary ur-trend pairs project to correspondingly arranged medial/ lateral ur-trend sequences in the neocortex. This pattern was previously shown to be in evidence for exteroceptive inputs projecting to posterior forebrain regions. This dual ur-trend pattern will also be shown to be a unifying principle for the class of interoceptive thalamic inputs as well.
In summary, The premotor area #6, similar to the primary motor region exhibits two maxima of koniocortical differentiation, areas # 6aα and # 6bα. Area # 6aα receives thalamic imput from nucleus ventro-oralis anterior end the adjacent portion of ventro-oralis internus, which, in turn, respectively receive input from the internal globus pallidus and the interstitial nucleus of Calal. Interconnections between the interstitial nucleus and the internal globus pallidus suggest that the pair might function as a common motor functional group. The rotary head movements elicited by stimulation of interstitial nucleus (Hassler 1972) together with its internal projection in the ventral-oral nucleus would suggest this component deals primarily with motor responses of the head. Movement involving the whole body during internal pallidar stimilation together with its more external ventro-oral projection suggests a reciprocal motor component dealing with trunk. Topographical criteria point to projections from nucleus zentro-oralis to area #6aβ, and from nucleus ventro-oralis medialis to area #6bβ. The other koniocortical maximum, # 6bα, is dysgranular in contrast to the more posterior agranular # 6aα. The incipient granularity of area # 6bα is not to be mistaken with Broca’s grnular opercular area (von Economo’s area FcBm). Area # 6bα has been demonstrated to receive imput from nucleus lateropolaris externus and internus. These thalamic nuclei have been shown to be the cortical relay for input from external segment of the globus pallidus (Hassler 1971). The praestitial nucleus of the midbrain projects to the internal lateropolar region (Hassler 1971) and also interconnects with the external segment of the globus pallidus. These observations suggest a praestitial pallidar functional motor unit analogous to that demonstrated in the case of the interstitial nucleus and the internal pallidum. The praestitial nucleus is the center for raising movements of the head in electrocorticel stimulation studies, further supporting this speculation. The dysgranular pleurokonio-area #6bβ ventrally borders on koniocortical area # 6bα. The thalamic relay nucleus for area #6bβ has been demonstrated to be nucleus lateropolaris basialis, which as the name implies, blends into the specific lateropolar segment ventrally. The upper pleurokonio-area, # 6aβ displays also an anterior dysgranular zone (Sanides 1964) completing the vertical granular band in area # 6. The nucleus lateropolaris superior, besides dorsally bordering on nucleus lateropolaris externus, has been cited as projecting to frontal and dorsal # 6aβ.
Although located in the telencephalon, the globus pallidus was shown in actuality to be a displaced diencephalic motor region. The interstitial and praestitial nuclei of the posterior commissure appear to be functionally related to the diencephalon rather than to the adjacent midbrain. Thus the pallidar imput complex represents the motor component of the class of intrinsic thalamic inputs. The corresponding cortical projection field is composed of agranular and dysgranular components corresponding to the # 6a and the # 6b premotor bands. Determination of the respective accentuated ur-trend is difficult also in the case of the premotor region. The parcellation schemes of Broadman and von Economo respectively identify the premotor region as areas #6 and FB, respectively. Vogt’s finer parcellation of area #6 is not sufficiently conclusive in terms of accentuation of the externa1 or internal pyramidal layers. Larger pyramidal cells in the internal pyramidal layer of the posterior premotor segment suggest a medial corticoid ur-trend applies to this region. This observation is consistent with the more dorsal location of # 6aα relative to area # 6bα. Close approximation of the more anteriorly situated # 6bα with the frontal operculum suggests lateral ur-trend of differentiation for this region.
THE INTEROCEPTIVE CLASS OF INPUTS
The final category of the parameter of input specificity concerns the class of interoceptive inputs. The term interceptive implies all aspects of the internal environment such as the visceral, digestive, and autonomic systems. Interoceptive input is relayed to the forebrain exclusively through the hypothalamus and the adjoining midbrain area. The hypothalamus has been appropriately termed the head ganglion of the autonomic nervous system in line with its modulating effect upon autonomic response. Different regions in the hypothalamus also have been implicated in the regulation of hunger, thirst, temperature, blood pressure, and sexual behavior. In addition, the high post thalamus displays an intimate association with the pituitary gland (the master gland of the endocrine system). The overwhelming importance of internal regulation has left the hypothalamus virtually unchanged over much of the phylogenetic scale of evolution. The neural circuitry of the hypothalamus correspondingly appears very diffuse and randomly organized in contrast to the directionally specific conductivity of the exteroceptive and proprioceptive inputs. This lack of specificity is structurally reflected in the main thalamic interoceptive terminus, the dorsomedial complex of nuclei.
The medial thalamic group in humans is a large ovoid complex of nuclei separated from the lateral thalamic complex by the internal medullary sheath of fibers. The medial group laterally borders the third ventricle and blends with the pulvinar at the caudal-most levels. The medial complex is more homogeneous in structure than the lateral group or the pulvinar, leading some researchers to simply designate the entire region as the dorsomedial thalamic nucleus. This overall cytoarchitectonic uniformity is most likely a result of the more diffuse distribution of the nonspecific interoceptive inputs. Through the use of additional myelographic techniques, however, Rolf Hassler was able to subdivide the medial group into four para-coronal planes analogous to the respective ur-trends of the lateral complex. The analysis of fiber patterns led Hassler (1959) to distinguish an anterior fascicular subdivision and a posterior caudal group of nuclei. The fascicular group is further subdivided by fiber variations into medialis fasciculosus anterior and medialis fasciculosus posterior. The fascicular nuclei also vary in the degree of differentiation along a medio-lateral gradient suggesting that these nuclei cover more than one growth shell. Hassler adds to this speculation by citing projections from medialis fasciculosus anterior to the orbito-frontal areas #11 and #12. Medialis fasciculosus posterior, in turn, projects to the more posterior prefrontal areas #46 and #10. Medial to the fascicular complex lies a region of denser single fiber architectonic termed medialis fibrosus.
The fibrosus subdivision coincides in the most part to the large celled cytoarchitectonic subdivision termed by most researchers the magnocellular dorsomedial nucleus. Nucleus medialis fibrosus also appears to cover more than one growth shell in light of the cited projections from this nucleus to areas FF and FI of the insular cortex (Yakolev, 1966). The pronounced concentration of larger cells in the antero-most part of medialis fibrosus (Van Buren, 1972) indicates that only the adjacent anterior subdivision of M. fasciculosus was derived across the epithalamic ur-trend spanning medialis fibrosus. This ur-trend is completed by the poorly differentiated nucleus medialis basiales, which correspondingly projects to the very oldest growth ring segment of the insular neocortex.
In contrast, the nucleus fasciculosus posterior evolved as the end result of a ventral ur-trend spanning parts of the anterior limbic nuclei of Yakolev (1966). The immediate precursor to medialis fasciculosus posterior appears to be nucleus antero-medialis situated as its name implies at the anterior pole of the human thalamus. This nucleus projects to the paralimbic area #32 on the medial aspect of the hemisphere (Hassler, 1959). At one age level fur¬ther removed one encounters the principle nucleus (Hassler’s Anteroventralis) also of the anterior nucleur complex. Nucleus anteroventralis projects to the limbic cortical area #24 of the anterior cingulate gyrus, confirming the anticipated connectivity between the composite multisensory growth shell and the proisocortex. The subthalamic ur-trend is completed by the nucleus antero-¬interior, which approaches the midline in close approximation to the antero¬reuniens subdivision of the primordial periventricular gray. Antero-interior projects to the periallocortical area #25 of the most ancient portion of the limbic cortex.
The dual trend origin of the fascicular complex closely parallels the similar phylogenetic development of the caudal group of the medial complex. This caudal group differs from its anterior counterpart in that the distinction between the fascicular and fibrous parts no longer is entirely apparent. Through cytoarchitectonic criteria, however, Hassler subdivided this region into nucleus medialis caudalis externus and medialis caudalis internus. The rather expansive medialis caudalis externus spans the most recent two growth shells consistent with its projection to koniocortical area #45 and prekoniocortical area #9 (Hassler, 1959). Nucleus medialis caudalis internus, in turn, extends across the remaining age levels of the dorsal ur-trend the project to area #47 and the older subdivisions of the anterior insular cortex.
The remaining subdivision of the caudal group corresponds to the conspicuously large-celled nucleus paralamellaris. As its name implies, paralamellaris is described as a prominent nucleus situated immediately subjacent to the external medullary lamina in the caudal-most quadrant of the medial group. Nucleus paralamellaris similarly spans the most recent two growth shells, projecting to both growth ring segments of the area #8 para-motor zone. The subthalamic ur-trend his continued under the guise of the nucleus medialis fasciculosus superior, situated, as its name implies, over the medial complex. This nucleus relays projections to the paralimbic area #32 of the medial frontal lobe. This thalamic ur-trend reaches its further extension as the nucleus anter-dorsalis, which projects to the frontal lobe portion of the cingulate gyrus.
The functional significance underlying the distinctive ur-trend pattern with respect to the medial complex is much less apparent than in the exteroceptive and proprioceptive regions. Hassler does not include an analysis of the medial complex in his hexapartition scheme, undoubtedly in recognition of the more diffuse character of the corresponding interoceptive classification of inputs. Specific terminations from the hypothalamus and the midbrain tegmental area are convincingly demonstrated only in the older (and characteristically less expansive) growth shells of the medial complex, but worthy input terminals are presumably more concentrated than at the more recent age levels. With regard to the intrinsic interceptive classification, the lateral subdivision of the hypothalamus was cited to connect with the magnocellular nucleus medialis (Nauta, 1971) of the epithalamic ur-trend, while the mammillary subdivision of the medial hypothalamus projects to the anterior thalamic group correspondingly situated with the subthalamic ur-trend. The extrinsic interoceptive input classification is represented by the thalamic projection of the group of midbrain tegmental nuclei loosely designated as the “limbic midbrain area” by Nauta (1958). Limbic midbrain projections to the more posterior parts of the medial complex have been cited from the interpeduncular nucleus (Massopust and Thompson, 1972) and from the midbrain tegmentum proper (Guillery, 1959).
In summary, the vastly expanded prefrontal granular cortex receives input exclusively from the dorsomedial thalamic nucleus (nucleus medialis of Hassler). The diffuse character of the interoceptive imput to the dorsomedial nucleus limits the proof of prefrontal input specificity to qualitative criteria. Interoceptive input to the nucleus medialis is composed of intrinsic and extrinsic thalamic components similar to that shown for the exteroceptive and motor input categories. The nucleus medialis is correspondingly subdivided into a pair of rostral and caudal basic subdivisions. The prefrontal cortex analogously also subdivisible into anterior and posterior constituent regions.
The posterior prefrontal cortex consists of the duplex of areas # 8 and # 9. Area # 9 consists of a pair of large and small celled prekonio—belt regions (Fdm, Fdp) surrounding the highly differentiated area #45 (pars triangularis of the inferior frontal gyrus). All three areas have been demonstrated to receive projections from the nucleus medialis caudalis externus and internus. The location of area #45 ventral to the limiting ur-trend sulcus, in addition to the presence of conspicuously large pyramidal cells in lamina IIIc, suggests a lateral ur-trend of development for this koniocortical representation. Posterior to area #9 lies the paramotor zone, medially to laterally composed areas # 8s, #8 and #44. Area #8s similar to area #4s is a dorsal prekonio- belt regarded as a suppressor of cortical activity in strychnine neuronographic studies. The ventral prekonio- area #44, situated on the inferior frontal gyrus should not be confused with the pars opercularis of area 6b-alpha. The pair of mirror-image frontal motor eye fields mapped by cortical stimulation overlap on the middle frontal gyrus (Crosby and Lauer, 1962) indicating a differentiation maximum in this part of area #8. This focal functional maximum dorsal to the ur-trend limiting sulcus suggests a medial ur-trend of development for the paramotor zone. All three pararnotor subareas have been cited to receive input from the nucleus medialis peralaminaris situated postero-laterally to medialis caudalis.
The anterior prefrontal region is composed of area # 10 and the orbito-frontal region area #10 consists of a pair of large and small celled prekonio- belt regions (Fe, Fem) bordering the highly differentiated koniocortical area #46, which is located dorsal to the ur-trend limiting sulcus, implying a medial ur-trend of differentiation. All three of these frontal subareas have been cited to receive input from the posterior portion of medialis fasciculosus and fibrosus. The orbital frontal region consists of area # 11 and area # 12 surrounding the highly differentiated pars orbitalis (area # 60 at Vogt’s terminology) of the inferior frontal gyrus. This set of areas has been demonstrated to receive input from the anterior segment of nucleus medialis faciculosus and fibrosus. Location of area pars orbitalis ventral to the ur-trend limiting sulcus, in addition to conspicuously large pyramidal cells in lamina IIIc, suggests a lateral ur-trend of development for this koniocortical representation.
DISCUSSION
The postulation of two basic parameters or forebrain evolution is fully substanllated in regard to fundamental neuroanatomical criteria. The cytoarchitectonic parcellations of both the thalamus and the cortex quantitatively define a direct function of the para¬meters of input specificity and phylogenetical age. Each cytoarchitec¬tonic subdivision is numerically correlated to a unique Cartesian coordinate value of discrete age and imput parameter levels. Thalamo-¬cortical projections prove to also corroborate the dual parameter paradigm. Thalarnic and cortical parcellation units of correspondingly identical basic parameter coordinates, demonstrate intrinsic interconnectivity across the internal capsule. This interconnectivity between topographically homologous forebrain levels, implies concomitant evolution of the thalamic and cortical age gradations.
The parameter of phylogenetic age is more readily apparent in the highly uniform planar pallium than in the three dimensional dorsal thalamus. The neopallium structurally evolves as an interlocking lamination of the superficial allocortical ring with the deep corticoid ring. The allocortical ring consists of a pair of paleocortical and archaecortical moieties. The former moiety is characteristically specific to main olfactory bulb imput while the latter appears similarly related to the accessory olfactory bulb. The corticoid ring is also divisible into “paleo” and “archae” moieties, however, with the principal input issuing from the dorsal thalamus rather than from the olfactory bulbs. In regard to more recent neopallial age levels, the term prekoniocortex was introduced to specify the presence of an additional circumferential wave, situated intermediate to Sanides’ paralimbic growth ring and the classical koniocortex.
At the diencephalic forebrain level, the concept of thalamic “growth shells” was introduced to define the circumfer¬ential age gradation in the dorsal thalamus, The primordial precursors of the dorsal thalamus are the subthalamic and epichalamic moieties receiving input from the lateral eyes and parietal eye respectively. Contrary to the age parameter, the parameter of input specificity is most clearly manifest in the dorsal thalamus of the forebrain. The cortex is one synaptic level removed from the inputs that terminate directly in the dorsal thalamus. Accordingly, the individual units of the parameter of input specificity are designated after those subcortical nuclei projecting discretely to circumscribed thalanic regions.
Each of the fourteen possible input units is classified according to exteroceptive, interoceptive or proprioceptive functional characteristics. Each of these three functional inout classifications is further divisible into a pair of diencephalically indigenous (intrinsic) and diencephalically extraneous (extrinsic) components. The class of extrinsic thalamlc input is distinct from the intrinsic classification In that it comprises the major afferent link between the forebrain and the remainder of the encephalon. Certain specific portions of the extrinsic input pathways appear only at the out¬set of mammalian evolution. The dentato-thalamic component of the cerebellar system and the dorsal column tracts of the somatosensory system began to evolve at a time when the circumfer¬ential age levels of the forebrain initially developed. This synchrony of the neuraxial evolution relative to the forebrain suggests that the parameter of phylogenetical age may prove applicable to the encephalon as a whole. Although exceedingly more complexity is entailed in distinguishing the six individual age divisions at the subforebrain level, the propitious accomplishment of such a feat would expand the role of the dual parameter paradigm into that of an integral and global definition of neuronal interconnectivity.
This tripartite pattern of connectivity between the exteroceptive, interoceptive, and motor cortical representations demonstrates a synaptic sequence analogous to that already demonstrated to occur between the functional columns of the neuraxial cord. Moreover, the intrinsic and extrinsic cortical categories each exhibit a tripartite pattern of long intercortical fibers in relation to one another. This observation is consistent with the similar segregation of intrinsic and extrinsic inputs in relation to their respective levels of the neuraxial spinal cord. Shorter intercortical fibers, however, freely cross this intrinsic/extrinsic functional barrier within their respective regions. For instance, all prefrontal areas are interconnected by short association fibers irrespective of their anterior-posterior orientation. A similar pattern of an interconnectivity occurs between the premotor and motor regions, as well as between the occipital, temporal, and parietal lobes.
Even the primordial allocortical moiety exhibits this basic tripartite pattern of interconnectivity. The archaecortex proper consists of the sensory-oriented dentate gyrus, the interoceptive regio inferior, and the motor regio superior. The dentate gyrus, which receives accessory olfactory bulb input, projects to the regio inferior of the cornu ammonis via the mossy fibers. The regio inferior, which has been electro-physiologically shown to pace the activity of the cells of the medial septum, projects to the regio superior by way of the Schaefer collaterals.
That has actually unified the spinal brainstem, thalamic and cortical levels of the neuraxis into common functional continuum. The rudimentary series of three functional laminae in the dorsal horn of the human spinal cord is dramatically amplified at higher levels to reach the dynamically complex 4:4:4 pattern of the human forebrain.
The actual exteroceptive-to-interoceptive-to-proprioceptive sequence of convergence expressed in the spinal cord unfortunately was not readily apparent in the brainstem or thalamus due to a combination of structural modifcations and/or technical difficulties. In the cortex however, both of these shortcomings are negligible, creating the ideal conditions for the demonstration of the cortical homologue of the three-way spinal convergence pattern. The surface configuration of the cortex allows individual regions to be selectively damaged without affecting either the surrounding regions of the underlying white matter. The selectively staining of degenerating axons from the destroyed cells often trace a looping course through the subcortical white matter on the way to terminate in more distant sites within the cortex. Many connections are seen as short loops linking adjacent gyri, in a type of localized integration of related functional regions. Well defined systems of longer fibers are also in evidence in the human hemisphere, linking the interoceptive prefrontal lobe with both the proprioceptive frontal lobe and the exteroceptive posterior lobes. These three cortical regions should demonstrate the same sequential order to of convergence previously established within the dorsal horn of the spinal cord. The ethical restrictions on the use of human subjects for anatomical experimentation is circumvented through the systematic investigation of mankind’s close relative, the rhesus monkey. The demonstration of a reciprocal type of interconnectivity linking the posterior cortical regions with the prefrontal zone, and in turn, the prefrontal zone the frontal region should verify the commensurability of the cortical and spinal models to an ever higher degree of confidence.
The mature pattern of human intercortical connectivity is first detected in the very earliest ages of the developing infant brain. The formation of inter-cerebral links during the first three years of the infancy was studied by a Khrizman using correlation analysis of EEG tracings taken from the frontal, precentral, parietal, temporal, and occipital lobes. The general overlapping pattern of fluctuating potentials between these five cortical areas in week-old resting infants was evident as a small complement (13 to 24%) of weak correlations. The most pronounced changes in the spatial distribution of integrated activity takes place in children between the ages of 14 months and three years. At that time, high correlations become more numerous and of particular significance, their focus, judging from the pattern of peak correlation paths, chefs from the posterior to the anterior association structures; namely, to the frontal lobes of the cortex. This functional shift is paralleled by a rapid growth spurt in the frontal lobes at two years of age (Kononova, 1965). According to Khrizman, this focal shift in integrative activity to the frontal lobes during the second year of life is a prominent manifestation of this accelerated phase of cerebral development. The frontal lobe has at this stage matured sufficiently to facilitate its role as intermediary in the intercortical relay sequence.
A parallel type of EEG analysis has been undertaken for adult subjects during both resting and active mental states. The total number of high value synchronous sites throughout the cortex was shown to dramatically increase during mental tasks, such as multiplying pairs of two digit numbers. The synchronously operating sites were found to be largely concentrated in the frontal lobes, verifying this regions pivotal significance in intercortical conductivity. Furthermore, there often occurs a synchrony between the prefrontal and motor cortex, indicating the convergence of the intermediate prefrontal link directly upon the motor end points within the hemisphere. The surgical isolation of the cortex from the functional influence of the subcortical centers disrupts the synchronization of brain wave activity within the hemisphere. This experimental observation verifies the major role that thalamo-cortical connections play in the maintenance of cortical synchronization. The thalamus correspondingly exhibits the same extero-intero-proprioceptive sequence of input convergence already shown to exist on the grand scale in the cortex. There is, however, a fundamental difference between these two major subdivisions of the forebrain that suggests that the cortex plays a much more dominant role in the functional unification of the forebrain than does the thalamus.
The cerebral hemispheres are linked by a massive system of commissural fibers that is completely lacking in the thalamus. This corpus callosum commissure is composed of approximately 200 million pyramidal cell axons that symmetrically interconnect mirror-image areas of each hemisphere. The informa¬tion capacity of the corpus callosum rivals even that of the long inter-cortical fibers linking the three basic functional regions of the cortex. These two types of fiber systems serve reciprocal functional roles: the intercortical fiber system integrates the functional subregion of each hemisphere, while the corpus callosum serves to keep the same functional areas of the different hemispheres in functional synchrony.