Laminar organization

The most apparent microscopical feature of the neocortex when it has been stained for cell bodies or for fibres is its horizontal lamination. The significance of this for understanding cortical functional organization is debatable, but the use of cytoarchitectonic description to identify regions of cortex is common.

Typical neocortex is described as having six layers or laminae lying parallel to the surface (Fig. 23.6).

Fig. 23.6 The layers of the cerebral cortex. The three vertical columns represent the disposition of cellular elements as revealed by the staining techniques of Golgi (impregnating whole neurones), Nissl (staining cell bodies) and Weigert (staining nerve fibres).

Five regional variations are described in neocortical structure (Fig. 23.7). While all are said to develop from the same six-layered pattern, two types, granular and agranular, are regarded as virtually lacking certain laminae, and are referred to as heterotypical. Homotypical variants, in which all six laminae are found, are called frontal, parietal and polar, names that link them with specific cortical regions in a somewhat misleading manner (e.g. the frontal type also occurs in parietal and temporal lobes).

Fig. 23.7 The distribution and characteristics of the five major types of cerebral cortex.

The agranular type is considered to have diminished, or absent, granular laminae (II and IV), but always contains scattered stellate somata. Large pyramidal neurones are found in the greatest densities in agranular cortex, which is typified by the numerous efferent projections of pyramidal cell axons. Although it is often equated with motor cortical areas such as the precentral gyrus (area 4), agranular cortex also occurs elsewhere, e.g. areas 6, 8 and 44 and parts of the limbic system.

In the granular type of cortex the granular layers are maximally developed, and contain densely packed stellate cells, among which small pyramidal neurones are dispersed. Laminae III and IV are poorly developed or unidentifiable. This type of cortex is particularly associated with afferent projections. However, it does receive efferent fibres, derived from the scattered pyramidal cells, although they are less numerous than elsewhere. Granular cortex occurs in the postcentral gyrus (somatosensory area), striate area (visual area) and superior temporal gyrus (acoustic area), and in small areas of the parahippocampal gyrus. Despite its very high density of stellate cells, especially in the striate area, it is almost the thinnest of the five main types. In the striate cortex the external band of Baillarger (lamina IV) is well defined as the stria (white line) of Gennari.

The other three types of cortex are intermediate forms. In the frontal type, large numbers of small- and medium-sized pyramidal neurones appear in laminae III and V, and granular layers (II and IV) are less prominent. The relative prominence of these major forms of neurone vary reciprocally wherever this form of cortex exists.

The parietal type of cortex contains pyramidal cells, which are mostly smaller in size than in the frontal type. In marked contrast, the granular laminae are wider and contain more of the stellate cells: this kind of cortex occupies large areas in the parietal and temporal lobes. The polar type is classically identified with small areas near the frontal and occipital poles and is the thinnest form of cortex. All six laminae are represented, but the pyramidal layer (III) is reduced in thickness and not so extensively invaded by stellate cells as it is in the granular type of cortex. In both polar and granular types, the multiform layer (VI) is more highly organized than in other types.

It is customary to refer to some discrete cortical territories not only by their anatomical location in relation to gyri and sulci, but also in relation to their cytoarchitectonic characteristics (Brodmann’s areas) (Fig. 23.8). Some of the areas so defined, e.g. the primary sensory and motor cortices, have clear relevance in terms of anatomical connections and functional significance, others less so.

Fig. 23.8 The lateral (A) and medial (B) surfaces of the left cerebral hemisphere depicting Brodmann’s areas.

Cortical lamination and cortical connections

The cortical laminae represent, to some extent, horizontal aggregations of neurones with common connections. This is most clearly seen in the lamination of cortical efferent (pyramidal) cells. The internal pyramidal lamina, layer V, gives rise to cortical projection fibres, most notably corticostriate, corticobulbar (including corticopontine) and corticospinal axons. In addition, a significant proportion of feedback corticocortical axons arise from cells in this layer, as do some corticothalamic fibres. Layer VI, the multiform lamina, is the major source of corticothalamic fibres. Supragranular pyramidal cells, predominantly layer III, but also lamina II, give rise primarily to both association and commissural corticocortical pathways. Generally, short corticocortical fibres arise more superficially, and long corticocortical (both association and commissural) axons come from cells in the deeper parts of layer III. Major afferents to a cortical area tend to terminate in layers I, IV and VI. Quantitatively lesser projections end either in the intervening laminae II/III and V, or sparsely throughout the depth of the cortex. Numerically, the largest input to a cortical area tends to terminate mainly in layer IV. This pattern of termination is seen in the major thalamic input to visual and somatic sensory cortex. In general, non-thalamic subcortical afferents to the neocortex, which are shared by widespread areas, tend to terminate throughout all cortical layers, but the laminar pattern of their endings still varies considerably from area to area.

Columns and modules

Experimental physiological and connectional studies have demonstrated an internal organization of the cortex, which is at right angles to the pial surface, with vertical columns or modules running through the depth of the cortex. The term ‘column’ refers to the observation that all cells encountered by a microelectrode penetrating and passing perpendicularly through the cortex respond to a single peripheral stimulus, a phenomenon first identified in the somatosensory cortex. In the visual cortex, narrow (50 μm) vertical strips of neurones respond to a bar stimulus of the same orientation (orientation columns) and wider strips (500 μm) respond preferentially to stimuli detected by one eye (ocular dominance columns). Adjacent orientation columns aggregate within an ocular dominance column to form a hypercolumn, responding to all orientations of stimulus for both eyes for one point in the visual field. Similar functional columnar organization has been described in widespread areas of neocortex, including motor cortex and association areas.

Primary motor cortex

The primary motor cortex (MI) corresponds to the precentral gyrus (area 4), and is the area of cortex with the lowest threshold for eliciting contralateral muscle contraction by electrical stimulation. It contains a detailed topographically organized map (motor homunculus) of the opposite body half, with the head represented most laterally, and the leg and foot represented on the medial surface of the hemisphere in the paracentral lobule (Fig. 23.9). A striking feature is the disproportionate representation of body parts in relation to their physical size: large areas represent the muscles of the face and hand, which are capable of finely controlled or fractionated movements.

Fig. 23.9 A, The motor homunculus showing proportional somatotopical representation in the main motor area. B, The sensory homunculus showing proportional somatotopical representation in the somaesthetic cortex.

The cortex of area 4 is agranular, and layers II and IV are difficult to identify. The most characteristic feature is the presence in lamina V of some extremely large pyramidal cell bodies, Betz cells, which may approach 80 μm in diameter. These neurones project their axons into the corticospinal and corticobulbar tracts.

The major thalamic connections of area 4 are with the ventral posterolateral nucleus (VPL), which in turn receives afferents from the deep cerebellar nuclei. The VPL nucleus also contains a topographic representation of the contralateral body, which is preserved in its point-to-point projection to area 4, where it terminates largely in lamina IV. Other thalamic connections of area 4 are with the centromedian and parafascicular nuclei. These appear to provide the only route through which output from the basal ganglia, routed via the thalamus, reaches the primary motor cortex, since the projection of the internal segment of the globus pallidus to the ventrolateral nucleus of the thalamus is confined to the anterior division, and there is no overlap with cerebellothalamic territory. The anterior part of the ventrolateral nucleus projects to the premotor and supplementary motor areas of cortex with no projection to area 4.

The ipsilateral somatosensory cortex (SI) projects in a topographically organized way to area 4, and the connection is reciprocal. The projection to the motor cortex arises in areas 1 and 2, with little or no contribution from area 3b. Fibres from SI terminate in layers II and III of area 4, where they contact mainly pyramidal neurones. Evidence suggests that neurones activated monosynaptically by fibres from SI, as well as those activated polysynaptically, make contact with layer V pyramidal cells, including Betz cells, which give rise to corticospinal fibres. Movement-related neurones in the motor cortex which can be activated from SI tend to have a late onset of activity, mainly during the execution of movement. It has been suggested that this pathway plays a role primarily in making motor adjustments during a movement. Additional ipsilateral corticocortical fibres to area 4 from behind the central sulcus come from the second somatic sensory area (SII).

Neurones in area 4 are responsive to peripheral stimulation, and have receptive fields similar to those in the primary sensory cortex. Cells located posteriorly in the motor cortex have cutaneous receptive fields, whereas more anteriorly situated neurones respond to stimulation of deep tissues.

The motor cortex receives major frontal lobe association fibres from the premotor cortex and the supplementary motor area and also fibres from the insula. It is probable that these pathways modulate motor cortical activity in relation to the preparation, guidance and temporal organization of movements. Area 4 sends fibres to, and receives fibres from, its contralateral counterpart, and also projects to the contralateral supplementary motor cortex.

Apart from its contribution to the corticospinal tract, the motor cortex has diverse subcortical projections. The connections to the striatum and pontine nuclei are heavy. It also projects to the subthalamic nucleus. The motor cortex sends projections to all nuclei in the brain stem, which are themselves the origin of descending pathways to the spinal cord, namely the reticular formation, the red nucleus, the superior colliculus, the vestibular nuclei and the inferior olivary nucleus.

Premotor cortex

Immediately in front of the primary motor cortex lies Brodmann’s area 6. It extends onto the medial surface, where it becomes contiguous with area 24 in the cingulate gyrus, anterior and inferior to the paracentral lobule. A number of functional motor areas are contained within this cortical region. Lateral area 6, the area over most of the lateral surface of the hemisphere, corresponds to the premotor cortex.

The premotor cortex is divided into a dorsal and a ventral area (PMd and PMv respectively) on functional grounds, and on the basis of ipsilateral corticocortical association connections.

The major thalamic connections of the premotor cortex are with the anterior division of the ventrolateral nucleus and with the centromedian, parafascicular and centrolateral components of the intralaminar nuclei. Subcortical projections to the striatum and pontine nuclei are prominent, and this area also projects to the superior colliculus and the reticular formation. Both dorsal and ventral areas contribute to the corticospinal tract. Commissural connections are with the contralateral premotor, motor and superior parietal (area 5) cortex. Ipsilateral corticocortical connections with area 5 in the superior parietal cortex, and inferior parietal area 7b are common to both dorsal and ventral subdivisions of the premotor cortex, and both send a major projection to the primary motor cortex. The dorsal premotor area also receives fibres from the posterior superior temporal cortex and projects to the supplementary motor cortex. The frontal eye field (area 8) projects to the dorsal subdivision. Perhaps the greatest functionally significant difference in connectivity between the two premotor area subdivisions is that the dorsal premotor area receives fibres from the dorsolateral prefrontal cortex, whereas the ventral subdivision receives fibres from the ventrolateral prefrontal cortex. All of these association connections are likely to be, or are known to be, reciprocal.

Neuronal activity in the premotor cortex in relation to both preparation for movement and movement itself has been extensively studied experimentally. Direction selectivity for movement is a common feature of many premotor neurones. In behavioural tasks, neurones in the dorsal premotor cortex show anticipatory activity and task-related discharge as well as direction selectivity, but little or no stimulus-related changes. The dorsal premotor cortex is probably important in establishing a motor set or intention, contributing to motor preparation in relation to internally guided movement. In contrast, ventral premotor cortex is more related to the execution of externally (especially visually) guided movements in relation to a specific external stimulus.

Frontal eye field

The frontal eye field corresponds to parts of Brodmann’s areas 6, 8 and 9 (Fig. 23.10). It receives its major thalamic projection from the parvocellular mediodorsal nucleus, with additional afferents from the medial pulvinar, the ventral anterior nucleus and the suprageniculate–limitans complex, and connects with the paracentral nucleus of the intralaminar group. The thalamocortical pathways to the frontal eye field form part of a pathway from the superior colliculus, the substantia nigra and the dentate nucleus of the cerebellum. The frontal eye field has extensive ipsilateral corticocortical connections, receiving fibres from several visual areas in the occipital, parietal and temporal lobes, including the medial temporal area (V5) and area 7a. There is also a projection from the superior temporal gyrus, which is auditory rather than visual in function. From within the frontal lobe, the frontal eye field receives fibres from the ventrolateral and dorsolateral prefrontal cortices. It projects to the dorsal and ventral premotor cortices and to the medial motor area, probably to the supplementary eye field adjacent to the supplementary motor area proper. It projects prominently to the superior colliculus, to the pontine gaze centre within the pontine reticular formation, and to other oculomotor related nuclei in the brain stem. As its name implies, it is important in the control of eye movements.

Fig. 23.10 Lateral surface of the left cerebral hemisphere showing the frontal eye field (parts of areas 6, 8, 9), the motor speech (Broca’s) area (areas 44, 45) and Wernicke’s area. The perimeter of these areas is delineated by an interrupted line to indicate uncertainty as to their precise extent. Wernicke’s area is variously depicted by different authorities as encompassing a large parietotemporal area which includes areas 39 and 40. Areas 22 and 37 are considered by some to be respectively auditory and visuo-auditory areas associated with speech and language.

Supplementary motor cortex

The supplementary motor area (SMA; MII) lies medial to area 6, and extends from the most superolateral part to the medial surface of the hemisphere. Area 24 in the cingulate gyrus adjacent to area 6 contains several motor areas, which are termed cingulate motor areas. An additional functional subdivision, the preSMA, lies anterior to the supplementary motor area on the medial surface of the cortex. In the present discussion, these additional medial motor areas are included with the supplementary motor cortex.

The supplementary motor area receives its major thalamic input from the anterior part of the ventral lateral nucleus, which in turn is the major recipient of fibres from the internal segment of the globus pallidus. Additional thalamic afferents are from the ventral anterior nucleus, the intralaminar nuclei, notably the centrolateral and centromedial nuclei, and also from the mediodorsal nucleus. The connections with the thalamus are reciprocal. The supplementary motor cortex receives connections from widespread regions of the ipsilateral frontal lobe, including from the primary motor cortex, the dorsal premotor area, the dorsolateral and ventrolateral prefrontal, medial prefrontal and orbitofrontal cortex and the frontal eye field. These connections are reciprocal, but the major ipsilateral efferent pathway is to the motor cortex. Parietal lobe connections of the supplementary motor cortex are with the superior parietal area 5 and possibly inferior parietal area 7b. Contralateral connections are with the supplementary motor area, and motor and premotor cortices of the contralateral hemisphere. Subcortical connections, other than with the thalamus, pass to the striatum, subthalamic nucleus and pontine nuclei, the brain stem reticular formation and the inferior olivary nucleus. The supplementary motor area makes a substantial contribution to the corticospinal tract, contributing as much as 40% of the fibres from the frontal lobe.

The supplementary motor area contains a representation of the body in which the leg is posterior and the face anterior, with the upper limb between them. Its role in the control of movement is primarily in complex tasks which require temporal organization of sequential movements and in the retrieval of motor memory.

Stimulation of the supplementary motor area in conscious patients has been reported to elicit the sensation of an urge to move, or of anticipation that a movement is about to occur. A region anterior to the supplementary motor area for face representation (areas 44, 45) is important in vocalization and speech production (Fig. 23.10).

Prefrontal cortex

The prefrontal cortex on the lateral surface of the hemisphere comprises predominantly Brodmann’s areas 9, 46 and 45 (Fig. 23.8). In non-human primates, two subdivisions of the lateral prefrontal cortex are recognized, a dorsal area equivalent to area 9, and perhaps including the superior part of area 46, and a ventral area, consisting of the inferior part of area 46 and area 45. Areas 44 and 45 are particularly notable in man since, in the dominant hemisphere, they constitute the motor speech area (Broca’s area). Both the dorsolateral and ventrolateral prefrontal areas receive their major thalamic afferents from the mediodorsal nucleus, and there are additional contributions from the medial pulvinar, the ventral anterior nucleus and from the paracentral nucleus of the anterior intralaminar group. The dorsolateral area receives long association fibres from the posterior and middle superior temporal gyrus (including auditory association areas), from parietal area 7a, and from much of the middle temporal cortex. From within the frontal lobe it also receives projections from the frontal pole (area 10), and from the medial prefrontal cortex (area 32) on the medial surface of the hemisphere. It projects to the supplementary motor area, the dorsal premotor cortex and the frontal eye field. All these thalamic and corticocortical connections are reciprocal. Commissural connections are with the homologous area, and with the contralateral inferior parietal cortex. The ventrolateral prefrontal area receives long association fibres from both area 7a and area 7b of the parietal lobe, from auditory association areas of the temporal operculum, from the insula and from the anterior part of the lower bank of the superior temporal sulcus. From within the frontal lobe it receives fibres from the anterior orbitofrontal cortex and projects to the frontal eye field and the ventral premotor cortex. It connects with the contralateral homologous area via the corpus callosum. These connections are probably all reciprocal.

The cortex of the frontal pole (area 10) receives thalamic input from the mediodorsal nucleus, the medial pulvinar and the paracentral nucleus. It is reciprocally connected with the cortex of the temporal pole, the anterior orbitofrontal cortex, and the dorsolateral prefrontal cortex. The orbitofrontal cortex connects with the mediodorsal, anteromedial, ventral anterior, medial pulvinar, paracentral and midline nuclei of the thalamus. Cortical association pathways come from the inferotemporal cortex, the anterior superior temporal gyrus and the temporal pole. Within the frontal lobe it has connections with the medial prefrontal cortex, the ventrolateral prefrontal cortex and medial motor areas. Commissural and other connections follow the general pattern for all neocortical areas.