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.

The medial prefrontal cortex is connected with the mediodorsal, ventral anterior, anterior medial pulvinar, paracentral, midline and suprageniculate–limitans nuclei of the thalamus. It receives fibres from the anterior cortex of the superior temporal gyrus. Within the frontal lobe, it has connections with the orbitofrontal cortex, and the medial motor areas of the dorsolateral prefrontal cortex.

Somatosensory cortex

The postcentral gyrus corresponds to the primary somtosensory cortex (SI; Brodmann’s areas 3a, 3b, 1 and 2). Area 3a lies most anteriorly, apposing area 4, the primary motor cortex of the frontal lobe; area 3b is buried in the posterior wall of the central sulcus; area 1 lies along the posterior lip of the central sulcus; and area 2 occupies the crown of the postcentral gyrus.

The primary somatosensory cortex contains within it a topographical map of the contralateral half of the body. The face, tongue and lips are represented inferiorly, the trunk and upper limb are represented on the superolateral aspect, and the lower limb on the medial aspect of the hemisphere, giving rise to the familiar ‘homunculus’ map (Fig. 23.9).

The somatosensory properties of SI depend on its thalamic input from the ventral posterior nucleus of the thalamus, which in turn receives the medial lemniscal, spinothalamic and trigeminothalamic pathways. The nucleus is divided into a ventral posterolateral part, which receives information from the trunk and limbs, and a ventral posteromedial part, in which the head is represented. Within the ventral posterior nucleus, neurones in the central core respond to cutaneous stimuli and those in the most dorsal anterior and posterior parts, which arch as a ‘shell’ over this central core, respond to deep stimuli. This is reflected in the differential projections to SI: the cutaneous central core projects to 3b, the deep tissue-responsive neurones send fibres to areas 3a and 2, and an intervening zone projects to area 1. Within the ventral posterior nucleus, anteroposterior rods of cells respond with similar modality and somatotopic properties. They appear to project to restricted focal patches in SI of approximately 0.5 mm width, which form narrow strips mediolaterally along SI. The laminar termination of thalamocortical axons from the ventral posterior nucleus is different in the separate cytoarchitectonic subdivisions of SI. In 3a and 3b, these axons terminate mainly in layer IV and the adjacent deep part of layer III, whereas in areas 1 and 2 they end in the deeper half of layer III, avoiding lamina IV. Additional thalamocortical fibres to SI arise from the intralaminar system, notably the centrolateral nucleus.

There is a complex internal connectivity within SI. An apparently stepwise hierarchical progression of information processing occurs from area 3b through area 1 to area 2. Outside the postcentral gyrus, SI has ipsilateral corticocortical association connections with a second somatosensory area (SII); area 5 in the superior parietal lobe; area 4, the motor cortex, in the precentral gyrus; and the supplementary motor cortex in the medial part of area 6 of the frontal lobe.

SI has reciprocal commissural connections with its contralateral homologue, with the exception that the cortices containing the representation of the distal extremities are relatively devoid of such connections. Callosal fibres in SI arise mainly from the deep part of layer III and terminate in layers I to IV. Pyramidal cells contributing callosal projections receive monosynaptic thalamic and commissural connections.

SI has reciprocal subcortical connections with the thalamus and claustrum, and receives afferents from the basal nucleus of Meynert, the locus coeruleus and the midbrain raphe. It has other prominent subcortical projections. Corticostriatal fibres, arising in layer V, pass mainly to the putamen of the same side. Corticopontine and corticotectal fibres from SI arise in layer V. SI projects to the main pontine nuclei, and to the pontine tegmental reticular nucleus. In addition, axons arising in SI pass to the dorsal column nuclei and the spinal cord. Corticospinal pyramidal cells are found in layer V of SI. The topographical representation in the cortex is preserved in terms of the spinal segments to which different parts of the postcentral gyrus project. Thus, the arm representation projects to the cervical enlargement, the leg representation to the lumbosacral enlargement, and so on. Within the grey matter of the spinal cord, fibres from SI terminate in the dorsal horn, in Rexed’s laminae 3 to 5: fibres from 3b and 1 end more dorsally, and those from area 2 more ventrally.

The second somatosensory area (SII) lies along the upper bank of the lateral fissure, posterior to the central sulcus. SII contains a somatotopic representation of the body, with the head and face most anteriorly, adjacent to SI, and the sacral regions most posteriorly. SII is reciprocally connected with the ventral posterior nucleus of the thalamus in a topographically organized fashion. Some thalamic neurones probably project to both SI and SII via axon collaterals. Other thalamic connections of SII are with the posterior group of nuclei and with the intralaminar central lateral nucleus. SII also projects to laminae IV to VII of the dorsal horn of the cervical and thoracic spinal cord, the dorsal column nuclei, the principal trigeminal nucleus, and the periaqueductal grey matter of the midbrain.

Within the cortex, SII is reciprocally connected with SI in a topographically organized manner, and projects to the primary motor cortex. SII also projects in a topographically organized way to the lateral part of area 7 (area 7b) in the superior parietal lobe, and makes connections with the posterior cingulate gyrus. Both right and left SII areas are interconnected across the corpus callosum, although distal limb representations are probably excluded. There are additional callosal projections to SI and area 7b.

Experimental studies show that neurones in SII respond particularly to transient cutaneous stimuli, e.g. brush strokes or tapping, which are characteristic of the responses of Pacinian corpuscles in the periphery. They show little response to maintained stimuli.

Superior and inferior parietal lobules

Posterior to the postcentral gyrus, the superior part of the parietal lobe is composed of areas 5, 7a and 7b (Fig. 23.8). Area 5 receives a dense feedforward projection from all cytoarchitectonic areas of SI in a topographically organized manner. The thalamic afferents to this area come from the lateral posterior nucleus and from the central lateral nucleus of the intralaminar group. Ipsilateral corticocortical fibres from area 5 go to area 7, the premotor and supplementary motor cortices, the posterior cingulate gyrus, and the insular granular cortex. Commissural connections between area 5 on both sides tend to avoid the areas of representation of the distal limbs. The response properties of cells in area 5 are more complex than in SI, with larger receptive fields and evidence of submodality convergence. Area 5 contributes to the corticospinal tract.

In non-human primates, the inferior parietal lobe is area 7. In man, this area is more superior, and areas 39 and 40 intervene inferiorly. The counterparts for the latter areas in monkeys are unclear and little experimental evidence is available on their connections and functions. Their role in human cerebral processing is discussed below. In the monkey, area 7b receives somatosensory inputs from area 5 and SII. Connections pass to the posterior cingulate gyrus (area 23), insula and temporal cortex. Area 7b is reciprocally connected with area 46 in the prefrontal cortex and the lateral part of the premotor cortex. Commissural connections of area 7b are with the contralateral homologous area, and with SII, the insular granular cortex and area 5. Thalamic connections are with the medial pulvinar nucleus and the intralaminar paracentral nucleus.

In monkeys, area 7a is not related to the cortical pathways for somatosensory processing, but instead forms part of a dorsal cortical pathway for spatial vision. The major ipsilateral corticocortical connections to area 7a are derived from visual areas in the occipital and temporal lobes. In the ipsilateral hemisphere, area 7a has connections with the posterior cingulate cortex (area 24) and with areas 8 and 46 of the frontal lobe. Commissural connections are with its contralateral homologue. Area 7a is connected with the medial pulvinar and intralaminar paracentral nuclei of the thalamus. In experimental studies, neurones within area 7a are visually responsive: they relate largely to peripheral vision, respond to stimulus movement, and are modulated by eye movement.

Auditory cortex

The temporal operculum houses the primary auditory cortex, AI. This is coextensive with the granular area 41 in the transverse temporal gyri. Surrounding areas constitute auditory association cortex. The primary auditory cortex is reciprocally connected with all subdivisions of the medial geniculate nucleus, and may receive additional thalamocortical projections from the medial pulvinar. The geniculocortical fibres terminate densely in layer IV. AI contains a tonotopic representation of the cochlea in which high frequencies are represented posteriorly, and low frequencies anteriorly. Single-cell responses are to single tones of a narrow frequency band. Cells in single vertical electrode penetrations share an optimum frequency response.

The auditory cortex interconnects with prefrontal cortex, though the projections from AI are small. In general, posterior parts of the operculum project to areas 8 and 9. Central parts project to areas 8, 9 and 46. More anterior regions project to areas 9 and 46, to area 12 on the orbital surface of the hemisphere, and to the anterior cingulate gyrus on the medial surface. Contralateral corticocortical connections are with the same and adjacent regions in the other hemisphere. Onward connections of the auditory association pathway converge with those of the other sensory association pathways in cortical regions within the superior temporal sulcus.

Evidence suggests that area 21, the middle temporal cortex, is polysensory in man, and that it connects with auditory, somatosensory and visual cortical association pathways. The auditory association areas of the superior temporal gyrus project in a complex ordered fashion to the middle temporal gyrus, as does the parietal cortex. The middle temporal gyrus connects with the frontal lobe: the most posterior parts project to posterior prefrontal cortex, areas 8 and 9, while intermediate regions connect more anteriorly with areas 19 and 46. Further forwards, the middle temporal region has connections with anterior prefrontal areas 10 and 46, and with anterior orbitofrontal areas 11 and 14. The most anterior middle temporal cortex is connected with the posterior orbitofrontal cortex, area 12, and with the medial surface of the frontal pole. Further forwards, this middle temporal region projects to the temporal pole and the entorhinal cortex. Thalamic connections are with the pulvinar nuclei and the intralaminar group. Other subcortical connections follow the general pattern for all cortical areas. Some projections (e.g. to the pons), particularly from anteriorly in the temporal lobe, are minimal. Physiological responses of cells in this middle temporal region show convergence of different sensory modalities, and many neurones respond to faces.

The inferior temporal cortex, area 20, is a higher visual association area. The posterior inferior temporal cortex receives major ipsilateral corticocortical fibres from occipitotemporal visual areas, notably V4. It contains a coarse retinotopic representation of the contralateral visual field, and sends a major feedforward pathway to the anterior part of the inferior temporal cortex. The anterior inferior temporal cortex projects onto the temporal pole and to paralimbic areas on the medial surface of the temporal lobe. Additional ipsilateral association connections of the inferior temporal cortex are with the anterior middle temporal cortex, in the walls of the superior temporal gyrus, and with visual areas of the parietotemporal cortex. Frontal lobe connections are with area 46 in the dorsolateral prefrontal cortex (posterior inferior temporal), and with the orbitofrontal cortex (anterior inferior temporal). The posterior area also connects with the frontal eye field. Reciprocal thalamic connections are with the pulvinar nuclei; the posterior part is related mainly to the inferior and lateral nuclei, and the anterior part to the medial and adjacent lateral pulvinar. Intralaminar connections are with the paracentral and central medial nuclei. Other subcortical connections conform to the general pattern of all cortical regions. Callosal connections are between corresponding areas and the adjacent visual association areas of each hemisphere.

The cortex of the temporal pole receives feedforward projections from widespread areas of temporal association cortex which are immediately posterior to it. The dorsal part receives predominantly auditory input from the anterior part of the superior temporal gyrus. The inferior part receives visual input from the anterior area of the inferior temporal cortex. Other ipsilateral connections are with the anterior insular, the posterior and medial orbitofrontal, and the medial prefrontal cortices. The temporal pole projects onwards into limbic and paralimbic areas. Thalamic connections are mainly with the medial pulvinar nucleus, and with intralaminar and midline nuclei. Other subcortical connections are as for the cortex in general, although some projections, such as that to the pontine nuclei, are very small. Physiological responses of cells in this and more medial temporal cortex correspond particularly to behavioural performance and to the recognition of high-level aspects of social stimuli.

Nuclei of the amygdala project to, and receive fibres from, neocortical areas, predominantly of the temporal lobe, and possibly inferior parietal cortex. The density of these pathways increases towards the temporal pole.

Claustrum

The claustrum (see Fig. 23.27) is a thin sheet of grey matter lying deep to the insula. It is approximately coextensive with the insula, from which it is separated by the extreme capsule. Medially, the claustrum is separated from the putamen by the external capsule. It is thickest anteriorly and inferiorly, where it becomes continuous with the anterior perforated substance, amygdala and prepiriform cortex. In animals, it has reciprocal, topographically organized, connections with many regions of the neocortex. Little is known about the connections and functional significance of the claustrum in the human brain.

Fig. 23.27 Superior aspect of a horizontal section through the left cerebral hemisphere.

Olfactory pathways

The organization of the olfactory system reflects its phylogenetically ancient lineage: afferent olfactory pathways proceed directly to the cerebral cortex, bypassing the thalamus, and its terminal fields are primitive cortical areas that are considered to be parts of the limbic system. Details of the relationship between the olfactory pathways and the limbic system are shown in Fig. 23.4.

The olfactory nerves arise from olfactory receptor neurones in the olfactory mucosa (see Ch. 32). The axons collect into numerous small bundles ensheathed by a population of unique glia and surrounded by layers of meninges, and enter the anterior cranial fossa by passing through the foramina in the cribriform plate of the ethmoid bone. They attach to the inferior surface of the olfactory bulb, which is situated at the anterior end of the olfactory sulcus on the orbital surface of the frontal lobe, and terminate in the bulb. Olfactory receptor neurones are continually replaced throughout life by differentiation of stem cells in the olfactory mucosa. The olfactory bulb is continuous posteriorly with the olfactory tract, through which the output of the bulb passes directly to the olfactory cortex.

There is a clear laminar structure in the olfactory bulb (Fig. 23.14). From the surface inwards the laminae are the olfactory nerve layer, glomerular layer, external plexiform layer, mitral cell layer, internal plexiform layer and granule cell layer. The olfactory nerve layer consists of the unmyelinated axons of the olfactory neurones. The continuous turnover of receptor cells means that axons in this layer are at different stages of growth, maturity or degeneration. The glomerular layer consists of a thin sheet of glomeruli where the incoming olfactory axons divide and synapse on terminal dendrites of secondary olfactory neurones, i.e. mitral, tufted and periglomerular cells. The external plexiform layer contains the principal and secondary dendrites of mitral and tufted cells. The mitral cell layer is a thin sheet composed of the cell bodies of mitral cells, each of which sends a single principal dendrite to a glomerulus, secondary dendrites to the external plexiform layer, and a single axon to the olfactory tract. It also contains a few granule cell bodies. The internal plexiform layer contains axons, recurrent and deep collaterals of mitral and tufted cells, and granule cell bodies. The granule cell layer contains the majority of the granule cells and their superficial and deep processes, together with numerous centripetal and centrifugal nerve fibres which pass through the layer.

Fig. 23.14 Organization of the olfactory bulb.

The principal neurones in the olfactory bulb are the mitral and tufted cells: their axons form its output via the olfactory tract. These cells are morphologically similar and most use an excitatory amino acid, probably glutamate or aspartate, as their neurotransmitter. The mitral cell spans the layers of the bulb, and receives the sensory input superficially at its glomerular tuft. The axons of mitral and tufted cells appear to be parallel output pathways from the olfactory bulb.

The main types of interneurones in the olfactory bulb are the periglomerular cells and granule cells. The majority of periglomerular cells are dopaminergic (cell group A15), but some are GABAergic: their axons are distributed laterally and terminate within extraglomerular regions. Granule cells are similar in size to periglomerular cells. Their most characteristic feature is the absence of an axon, and they therefore resemble amacrine cells in the retina. Granule cells have two principal spine-bearing dendrites which pass radially in the bulb: they appear to be GABAergic. The granule cell is likely to be a powerful inhibitory influence on the output neurones of the olfactory bulb.

Centrifugal inputs to the olfactory bulb arise from a variety of central sites. Neurones of the anterior olfactory nucleus and collaterals of pyramidal neurones in the olfactory cortex project to the granule cells of the olfactory bulb. Cholinergic neurones in the horizontal limb nucleus of the diagonal band of Broca, part of the basal forebrain cholinergic system, project to the granule cell layer and also to the glomerular layer. Other afferents to the granule cell layer and the glomeruli arise from the pontine locus coeruleus and the mesencephalic raphe nucleus.

The granule cell layer of the bulb is extended into the olfactory tract as scattered medium-sized multipolar neurones that constitute the anterior olfactory nucleus. Many centripetal axons from mitral and tufted cells relay in, or give collaterals to, the anterior olfactory nucleus; the axons from the nucleus continue with the remaining direct fibres from the bulb into the olfactory striae.

As the olfactory tract approaches the anterior perforated substance it flattens and splays out as the olfactory trigone. Fibres of the tract continue from the caudal angles of the trigone as diverging medial and lateral olfactory striae, which border the anterior perforated substance. The lateral olfactory stria follows the anterolateral margin of the anterior perforated substance to the limen insulae, where it bends posteromedially to merge with an elevated region, the gyrus semilunaris, at the rostral margin of the uncus in the temporal lobe. The lateral olfactory gyrus forms a tenuous grey layer covering the lateral olfactory stria: it merges laterally with the gyrus ambiens, part of the limen insulae. The lateral olfactory gyrus and gyrus ambiens form the prepiriform region of the cortex, passing caudally into the entorhinal area of the parahippocampal gyrus. The prepiriform and periamygdaloid regions and the entorhinal area (area 28) together make up the piriform cortex. The medial olfactory stria passes medially along the rostral boundary of the anterior perforated substance towards the medial continuation of the diagonal band of Broca. Together, they curve up on the medial aspect of the hemisphere, anterior to the attachment of the lamina terminalis.

The olfactory cortex receives a direct input from the olfactory bulb which arrives via the olfactory tract without relay in the thalamus. The largest cortical olfactory area is the piriform cortex. The anterior olfactory nucleus, olfactory tubercle, regions of the entorhinal and insular cortex and amygdala also receive direct projections from the olfactory bulb.

The entorhinal cortex (Brodmann’s area 28) is the most posterior part of the piriform cortex, and is divided into medial and lateral areas (areas 28a and 28b). The lateral parts receive fibres mainly from the olfactory bulb, and also from the piriform and periamygdaloid cortices.

Projections from the piriform olfactory cortex are widespread, and include the neocortex (especially the orbitofrontal cortex), thalamus (especially the medial dorsal thalamic nucleus), hypothalamus, amygdala and hippocampal formation.

Hippocampal formation

The hippocampal formation includes the dentate gyrus, hippocampus, subicular complex and entorhinal cortex.

The hippocampus lies above the subiculum and medial parahippocampal gyrus, forming a curved elevation, approximately 5 cm long, along the floor of the inferior horn of the lateral ventricle (Fig. 23.15). Its anterior end is expanded, and here its margin may present two or three shallow grooves that give a paw-like appearance, the pes hippocampi. The ventricular aspect is convex. It is covered by ependyma, beneath which fibres of the alveus converge medially on a longitudinal bundle of fibres, the fimbria of the fornix. Passing medially from the collateral sulcus, the neocortex of the parahippocampal gyrus merges with the transitional juxtallocortex of the subiculum (Fig. 23.16). The latter curves superomedially to the inferior surface of the dentate gyrus, then laterally to the laminae of the hippocampus. This curvature continues, first superiorly, then medially above the dentate gyrus, and ends pointing towards the centre of the superior surface of the dentate gyrus. The dentate gyrus is a crenated strip of cortex related inferiorly to the subiculum, laterally to the hippocampus and, more medially, to the fimbria of the fornix (Fig. 23.16, Fig. 23.17). The form of the fimbria is quite variable, but medially it is separated from the crenated medial margin of the dentate gyrus by the fimbriodentate sulcus (Fig. 23.18). The hippocampal sulcus, of variable depth, lies between the dentate gyrus and the subicular extension of the parahippocampal gyrus. Posteriorly, the dentate gyrus is continuous with the gyrus fasciolaris and thus with the indusium griseum. Anteriorly, it is continued into the notch of the uncus, turning medially across its inferior surface, as the tail of the dentate gyrus (band of Giacomini), and vanishes on the medial aspect of the uncus (Fig. 23.17). The tail separates the inferior surface of the uncus into an anterior uncinate gyrus and posterior intralimbic gyrus.

Fig. 23.15 Dissection of the left cerebral hemisphere demonstrating structures of the limbic system. The body of the corpus callosum has been divided sagitally. The frontal, temporal and occipital lobes have been sectioned horizontally and their superior parts removed. The left lentiform complex and thalamus have been removed and the floor of the inferior horn of the lateral ventricle opened.

(Dissection by AM Seal; photograph by Kevin Fitzpatrick on behalf of GKT School of Medicine, London; figure enhanced by B. Crossman.)

Fig. 23.16 Series of coronal sections of the temporal lobe and inferior horn of the lateral ventricle illustrating the relationships between the components of the hippocampal formation.

Fig. 23.17 Basal aspect of the brain dissected to display the dentate gyrus, uncus and fimbria on the left.

Fig. 23.18 The hippocampal formation showing the disposition of the various cell fields.

The trilaminar cortex of the dentate gyrus is the least complex of the hippocampal fields (Fig. 23.19). Its major cell type is the granule cell, found in the dense granule cell layer. Granule cells have unipolar dendrites that extend into the overlying molecular layer. The latter receives most of the afferent projections to the dentate gyrus, primarily from the entorhinal cortex (Fig. 23.20). The granule cell and molecular layers are sometimes referred to as the fascia dentata. The polymorphic layer, or hilus of the dentate gyrus, contains cells that give rise primarily to ipsilateral association fibres. They remain within the dentate gyrus and do not extend into other hippocampal fields.

Fig. 23.19 Coronal, thionin-stained section of the human hippocampal formation. Abbreviations: a, molecular layer of the dentate gyrus; b, granule cell layer of the dentate gyrus; c, plexiform layer of the dentate gyrus; CA1–3, fields of the hippocampus; d, stratum oriens layer of the hippocampus; DG, dentate gyrus; e, pyramidal cell layer of the hippocampus; EC, entorhinal cortex; f, stratum radiatum of the hippocampus; fim, fimbria; g, stratum lacunosum-molecular of the hippocampus; PaS, parasubiculum; PRC, perirhinal cortex; PrS, presubiculum; S, subiculum.

(By courtesy of D. Amaral.).

Fig. 23.20 Neuronal organization and connections of the dentate gyrus, hippocampus (cornu ammonis), subiculum and parahippocampal gyrus.

The hippocampus is trilaminar archicortex. It consists of a single pyramidal cell layer, with plexiform layers above and below it. It may best be divided into three distinct fields, CA1, CA2 and CA3 (Fig. 23.18, Fig. 23.19). Field CA3 borders the hilus of the dentate gyrus at one end, and field CA2 at the other. Field CA3 pyramidal cells are the largest in the hippocampus and receive the mossy fibre input from dentate granule cells on their proximal dendrites. The whole pyramidal cell layer in this field is about 10 cells thick. The border between CA3 and CA2 is not well marked. The CA2 field has the most compact layer of pyramidal cells. It completely lacks a mossy fibre input from dentate granule cells and receives a major input from the supramammillary region of the hypothalamus. Field CA1 is usually described as the most complex of the hippocampal subdivisions and its appearance varies along its transverse and rostrocaudal axes. The CA1/CA2 border is not sharp, and at its other end CA1 overlaps the subiculum for some distance. Approximately 10% of neurones in this field are interneurones.

It is common to describe several strata within the layers of the hippocampus. Starting from the ventricular aspect, these are the alveus (contains subicular and hippocampal pyramidal cell axons converging on the fimbria of the fornix); stratum oriens (mainly the basal dendrites of pyramidal cells and some interneurones); stratum pyramidalis; stratum lucidum (contains mossy fibres which make contact with the proximal dendrites of pyramidal cells in field CA3); and the stratum radiatum and stratum lacunosum-moleculare. The stratum lucidum is not as prominent in man as it is in other primates, and is not present in fields CA1 and CA2.

In the stratum radiatum and stratum oriens, CA3 and CA2 cells receive associational connections from other rostrocaudal levels of the hippocampus, as well as afferents from subcortical structures, e.g. the septal nuclei and supramammillary region. The projections from pyramidal cells of fields CA3 and CA2 to CA1, often called Schaffer collaterals, also terminate in the stratum radiatum and stratum oriens. The projections from the entorhinal cortex to the dentate gyrus (the perforant pathway) travel in the stratum lacunosum-moleculare, where they make synaptic contact en passant with the distal apical dendrites of hippocampal pyramidal cells.

The subicular complex is generally subdivided into subiculum, presubiculum and parasubiculum. The major subcortical projections of the hippocampal formation (to the septal nuclei, mammillary nuclei, nucleus accumbens and anterior thalamus), and to the entorhinal cortex, all arise from pyramidal neurones of the subicular complex. The subiculum consists of a superficial molecular layer containing apical dendrites of subicular pyramidal cells, a pyramidal cell layer, and a deep polymorphic layer. The presubiculum is medial to the subiculum and is distinguished by a densely packed superficial layer of pyramidal cells. It forms the boundary between the subicular complex as a whole and the entorhinal cortex. The cell layers deep to the parasubiculum are indistinguishable from the deep layers of the entorhinal cortex.

The entorhinal cortex (Brodmann’s area 28, Fig. 23.19) extends rostrally to the anterior limit of the amygdala. Caudally it overlaps a portion of the hippocampal fields. The more primitive levels of the entorhinal cortex (below the amygdala) receive projections from the olfactory bulb. More caudal regions do not generally receive primary olfactory inputs. The entorhinal cortex is divisible into six layers and is quite distinct from other neocortical regions. Layer I is acellular and plexiform. Layer II is a narrow cellular layer, which consists of islands of large pyramidal and stellate cells. These cell islands are a distinguishing feature of the entorhinal cortex. They form small bumps on the surface of the brain that can be seen by the naked eye (verrucae hippocampae), and provide an indication of the boundaries of the entorhinal cortex. Layer III consists of medium-sized pyramidal cells. There is no internal granular layer (another classic feature of entorhinal cortex); in its place is an acellular region of dense fibres called the lamina dissecans, which is sometimes called layer IV. Layers III and V are apposed in regions where the lamina dissecans is absent. Layer V consists of large pyramidal cells five or six deep. Layer VI is only readily distinguishable from layer V close to the border with the perirhinal cortex. Its cells continue around the angular bundle (subcortical white matter deep to the subicular complex made up largely of perforant path axons) to lie beneath the pre- and parasubiculum.

Glutamate and/or aspartate appears to be the major excitatory transmitter in three pathways in the hippocampal formation, namely the perforant pathway (which arises in the entorhinal cortex and terminates primarily in the dentate gyrus); the mossy fibres, which run from the dentate granule cells to the pyramidal cells of the CA3 field; and in the Schaffer collaterals of CA3 pyramidal cells, which terminate on CA1 pyramidal cells.

GABAergic neurones are found in the deep portions of the granule cell layer in the dentate gyrus (basket cells). The highest concentration of GABA receptors is found in the molecular layer of the dentate gyrus. In the hippocampus proper, GABAergic cells are found mostly in the stratum oriens, but also in the pyramidal cell layer and stratum radiatum.

There are many peptide-containing neurones in the hippocampal formation. Granule cells in the dentate gyrus appear to contain the opioid peptide dynorphin, which is also present in mossy fibres running to the CA3 field. Enkephalin, or a related peptide, may be present in fibres arising in the entorhinal cortex. There is a dense plexus of somatostatin-immunoreactive fibres in the molecular layer of the dentate gyrus and also in the stratum lacunosum-moleculare of the hippocampus. The polymorphic layer of the dentate gyrus, stratum oriens of the hippocampus and the deep layers of the entorhinal cortex, all contain somatostatin-immunoreactive neurones. Vasoactive intestinal polypeptide (VIP)-immunoreactive neurones are plentiful in many hippocampal fields, especially in the superficial layers of the entorhinal cortex. Cells containing cholecystokinin (CCK)-immunoreactivity are found in the hilar region of the dentate gyrus, in all layers of the hippocampus, especially in the pyramidal cell layer, and also throughout the subicular complex and entorhinal cortex. There are also substantial plexuses of CCK-immunoreactive fibres in the stratum lacunosum-moleculare, subicular complex and entorhinal cortex. Hippocampal CCK-immunoreactive cells may give rise to extrinsic projections, e.g. to the lateral septum and medial mammillary nucleus, because CCK-immunoreactive fibres are found in the fimbria/fornix.

The medial septal complex and the supramammillary area of the posterior hypothalamus are the two major sources of subcortical afferents to the hippocampal formation. There are also projections from the amygdaloid complex and claustrum (to the subicular complex and entorhinal cortex), as well as monoaminergic projections from the ventral tegmental area, the mesencephalic raphe nuclei and the locus coeruleus. The noradrenergic and serotoninergic projections reach all hippocampal fields, but are especially dense in the dentate gyrus.

The projections from the septal complex arise in the medial septal and vertical limb nuclei of the diagonal band. They travel via the dorsal fornix, fimbria, supracallosal striae and a ventral route through the amygdaloid complex. While these projections reach all hippocampal fields, the most prominent terminations are in the dentate gyrus, field CA3, presubiculum, parasubiculum and entorhinal cortex. Many of these medial septal/diagonal band neurones are GABAergic or cholinergic, and they form part of the topographically organized basal forebrain cholinergic system (cell groups Ch1 and Ch2).

Neurones in the supramammillary area also provide a significant innervation of the hippocampal formation. They arrive partly through the fornix and partly through a ventral route, and terminate most heavily in the dentate gyrus, and fields CA2 and CA3 of the cornu ammonis.

All divisions of the anterior thalamic nuclear complex and associated lateral dorsal nucleus project to the hippocampal formation, and are directed predominantly to the subicular complex. Some midline thalamic nuclei, particularly the parataenial, central medial and reuniens nuclei, also project to the hippocampal formation, especially to the entorhinal cortex.

The human fornix contains more than a million fibres. Cells in the CA3 field project bilaterally to the lateral nucleus of the septal complex, via the precommissural fornix. They give rise to the Schaffer collaterals to CA1 cells and to the commissural projections to the contralateral hippocampus. Neurones in the subicular complex and entorhinal cortex give rise to projections to the nucleus accumbens and to parts of the caudate nucleus and putamen. The subicular complex gives rise to the major, postcommissural fibre system of the fornix. The presubiculum, in particular, projects to the anterior thalamic nuclear complex (anteromedial, anteroventral and laterodorsal nuclei). Both the subiculum and presubiculum provide the major extrinsic input to the mammillary complex. Both the lateral and the medial mammillary nuclei receive afferents from the subicular complex.

Several fields in the temporal lobe neocortex, especially the parahippocampal gyrus, the dorsal bank of the superior temporal gyrus, the perirhinal cortex (Brodmann’s area 35) and the temporal polar cortex, together with the agranular insular cortex and posterior orbitofrontal cortex, project to the entorhinal cortex. Projections to the entorhinal cortex also arise from the dorsolateral prefrontal cortex (Brodmann’s areas 9, 10, 46), the medial frontal cortex (Brodmann’s areas 25, 32), the cingulate cortex (Brodmann’s areas 23, 24), and retrosplenial cortex. The subicular complex receives direct cortical inputs, e.g. from the temporal polar cortex, perirhinal cortex, parahippocampal gyrus, superior temporal gyrus and dorsolateral prefrontal cortex. The entorhinal cortex projects to the perirhinal cortex as well as to temporal polar cortex, caudal parahippocampal and cingulate gyri. In monkeys, the subicular complex also projects to a number of cortical areas, including perirhinal cortex, parahippocampal gyrus, caudal cingulate gyrus, medial frontal and medial orbitofrontal cortex.

Septum

The septum is a midline and paramedian structure (Fig. 23.13, Fig. 22.6). Its upper portion corresponds largely to the bilateral laminae of fibres, sparse grey matter and neuroglia, known as the septum pellucidum, which separates the lateral ventricles. Below this, the septal region is made up of four main nuclear groups: dorsal, ventral, medial and caudal. The dorsal group is essentially the dorsal septal nucleus, the ventral group consists of the lateral septal nucleus, the medial group contains the medial septal nucleus and the nucleus of the diagonal band of Broca, and the caudal group contains the fimbrial and triangular septal nuclei.

The major afferents to the region terminate primarily in the lateral septal nucleus. They include fibres carried in the fornix that arise from hippocampal fields CA3 and CA1 and the subiculum. There are also afferents arising from the preoptic area, anterior, paraventricular and ventromedial hypothalamic nuclei and the lateral hypothalamic area. The lateral septum receives a rich monaminergic innervation, including noradrenergic afferents from the locus coeruleus and medullary cell groups (A1, A2). It also receives serotoninergic afferents from the midbrain raphe nuclei and dopaminergic afferents from the ventral tegmental area (A10).

Projections from the lateral septum run to the medial and lateral preoptic areas, anterior hypothalamus, supramammillary and midbrain ventral tegmental area, via the medial forebrain bundle. There is also a projection to the medial habenular nucleus and some midline thalamic nuclei via the stria medullaris thalami, which runs on the dorsomedial wall of the third ventricle. The projections from the habenula via the fasciculus retroflexus to the interpeduncular nucleus and adjacent ventral tegmental area in the midbrain provide a route through which forebrain limbic structures can influence midbrain nuclear groups.

A large proportion of the medial septal/diagonal band neurones are cholinergic or GABAergic. They project to the hippocampal formation and cingulate cortex.

Amygdala

The amygdala (amygdaloid nuclear complex) consists of lateral, central and basal nuclei that lie in the dorsomedial temporal pole, anterior to the hippocampus, close to the tail of the caudate nucleus (Fig. 23.13) and partly deep to the gyrus semilunaris, gyrus ambiens and uncinate gyrus (Fig. 23.4). Collectively the nuclei form the ventral, superior and medial walls of the tip of the inferior horn of the lateral ventricle. The amygdala is partly continuous above with the inferomedial margin of the claustrum. Fibres of the external capsule and substriatal grey matter, including the cholinergic magnocellular nucleus basalis (of Meynert), incompletely separate it from the putamen and globus pallidus. Laterally, it is close to the optic tract.

The lateral nucleus has dorsomedial and ventrolateral subnuclei. The central nucleus has medial and lateral subdivisions. The basal nucleus is commonly divided into a dorsal magnocellular basal nucleus, an intermediate parvicellular basal nucleus, and a ventral band of darkly staining cells usually referred to as the paralaminar basal nucleus, because it borders the white matter ventral to the amygdaloid complex. The accessory basal nucleus lies medial to the basal nuclear divisions and is usually divided into dorsal, magnocellular, and ventral, parvicellular, parts. The lateral and basal nuclei are often referred to collectively as the basolateral area (nuclear group) of the amygdaloid complex.

It has been suggested that the basolateral complex of nuclei (lateral, basal, accessory basal) shares several characteristics with the cortex, and that it may be considered as a quasi-cortical structure. Although it lacks a laminar structure, it has direct, often reciprocal, connections with adjacent temporal and other areas of cortex, and it projects to the motor or premotor cortex. It receives a direct cholinergic and non-cholinergic input from the magnocellular corticopetal system in the basal forebrain, and has reciprocal connections with the mediodorsal thalamus. The distribution of small peptidergic neurones in the basolateral nuclear complex, e.g. those containing neuropeptide-Y (NY), somatostatin (SOM) and CCK, are also similar in form and density to those found in the adjacent temporal lobe cortex. Projection neurones from this part of the amygdala appear to utilize, at least in part, the excitatory amino acids glutamate or aspartate as a transmitter. Moreover, they project to the ventral striatum rather than to hypothalamic and brain stem sites. Thus, it may be appropriate to consider this part of the amygdaloid complex as a polymodal cortex-like area, separated from the cerebral cortex by fibres of the external capsule.

The central nucleus is present through the caudal half of the amygdaloid complex. It lies dorsomedial to the basal nucleus and is divided into medial and lateral parts. The medial part, which contains larger cells than the lateral part, resembles the adjacent putamen. The medial and central nuclei appear to have an extension across the basal forebrain, as well as within the stria terminalis, which merges with the bed nucleus of the stria terminalis. This extensive nuclear complex is sometimes referred to as the ‘extended amygdala’ (Fig. 23.21). It can be considered as a macrostructure formed by the centromedial amygdaloid complex (medial nucleus, medial and lateral parts of the central nucleus), the medial bed nucleus of the stria terminalis, and the cell columns that traverse the sublenticular substantia innominata, which lies between them. It has been suggested that portions of the medial nucleus accumbens may be included in the extended amygdala.

Fig. 23.21 Coronal section through the basal forebrain and temporal pole, illustrating the relationship between the striatum, nucleus accumbens, globus pallidus, ventral pallidum, extended amygdala and magnocellular basal forebrain system.

A consistent feature of the intrinsic connections among amygdaloid nuclei is that they arise primarily in lateral and basal nuclei, and terminate in the central and medial nuclei, which suggests a largely unidirectional flow of information. In brief, the lateral nucleus projects to all divisions of the basal nucleus, accessory basal nucleus, paralaminar and anterior cortical nuclei, and less heavily to the central nucleus: it receives few afferents from other nuclei. The magnocellular, parvicellular and intermediate parts of the basal nucleus project to the accessory basal, central (especially the medial part) and medial nuclei, as well as to the periamygdaloid cortex and the amygdalohippocampal area. The accessory basal nucleus projects densely to the central nucleus, especially its medial division, as well as to the medial and cortical nuclei. Its major intra-amygdaloid afferents arise from the lateral nucleus. The medial nucleus projects to the accessory basal, anterior cortical and central nuclei as well as to the periamygdaloid cortex and amygdalohippocampal area, while afferents arise especially from the lateral nucleus. The intrinsic connections of the cortical nucleus are not very well understood. The posterior part of the cortical nucleus projects to the medial nucleus, but it has been difficult to differentiate this projection from that arising in the amygdalohippocampal area. The central nucleus projects to the anterior cortical nucleus and the various cortical transition zones. It forms an important focus for afferents from many of the amygdaloid nuclei, especially the basal and accessory basal nuclei, and it has major extrinsic connections.

The organization of the extensive subcortical and cortical connections of the amygdala are consistent with a role in emotional behaviour. It receives highly processed unimodal and multimodal sensory information from the thalamus, sensory and association cortices; olfactory information from the olfactory bulb and piriform cortex; visceral and gustatory information relayed via brain stem structures and the thalamus. Its projections reach widespread areas of the brain, including the endocrine and autonomic domains of the hypothalamus and brain stem.

Corpus callosum

The corpus callosum (Fig. 23.2, Fig. 23.24, Fig. 23.25; see Fig. 22.2) is the largest fibre pathway of the brain. It links the cerebral cortex of the two cerebral hemispheres, and it roofs much of the lateral ventricles. It forms an arch approximately 10 cm long, with an anterior end approximately 4 cm from the frontal poles and a posterior end approximately 6 cm from the occipital poles. Its anterior portion is known as the genu. This recurves posteroinferiorly in front of the septum pellucidum, then diminishes rapidly in thickness and is prolonged to the upper end of the lamina terminalis as the rostrum. The trunk of the corpus callosum arches back and is convex above. It ends posteriorly in the expanded splenium, which is its thickest part.

Fig. 23.24 The superior aspect of the corpus callosum revealed by partial removal of the cerebral hemispheres.

Fig. 23.25 Anterior aspect of a coronal section of the cerebrum. The posterior parts of the thalami have been removed to reveal the splenium of the corpus callosum.

The median region of the trunk of the corpus callosum forms the floor of the great longitudinal fissure. Here, it lies close to the anterior cerebral arteries and the lower border of the falx cerebri, which may contact it behind. On each side, the trunk is overlapped by the cingulate gyrus, from which it is separated by the callosal sulcus. The inferior surface of the corpus callosum is concave in its long axis: it is attached to the septum pellucidum anteriorly and fused with the fornix and its commissure posteriorly.

The superior surface of the callosal trunk (Fig. 23.24) is covered by a thin layer of grey matter, the indusium griseum. This extends anteriorly around the genu and then continues into the paraterminal gyrus on the inferior aspect of the rostrum. It contains narrow longitudinal bundles of fibres on each side, the medial and lateral longitudinal striae. Posteriorly, the indusium griseum is continuous with the dentate gyrus and hippocampus through the gyrus fasciolaris (Fig. 23.25).

The splenium of the corpus callosum overhangs the posterior ends of the thalami, the pineal gland and tectum, but is separated from them by several structures. On each side the crus of the fornix and gyrus fasciolaris curve up to the splenium. The crus continues forwards on the inferior surface of the callosal trunk, but the gyrus fasciolaris skirts above the splenium, then rapidly diminishes into the indusium griseum. The tela choroidea of the third ventricle advances below the splenium through the transverse fissure, and the internal cerebral veins emerge between its two layers to form the great cerebral vein. Posteriorly the splenium is near the tentorium cerebelli, great cerebral vein and the start of the straight sinus.

Nerve fibres of the corpus callosum radiate into the white matter core of each hemisphere, thereafter dispersing to the cerebral cortex. Commissural fibres forming the rostrum extend laterally, below the anterior horn of the lateral ventricle, connecting the orbital surfaces of the frontal lobes. Fibres in the genu curve forwards, as the forceps minor, to connect the lateral and medial surfaces of the frontal lobes. Fibres of the trunk pass laterally, intersecting with the projection fibres of the corona radiata to connect wide neocortical areas of the hemispheres. Fibres of the trunk and splenium, which form the roof and lateral wall of the posterior horn and the lateral wall of the inferior horn of the lateral ventricle, constitute the tapetum. The remaining fibres of the splenium curve back into the occipital lobes as the forceps major.

Interhemispheric connections through the corpus callosum do not all represent a simple linking of loci in one hemisphere with the same loci in the other. In areas containing a clear representation of a contralateral sensorium (e.g. body surface, visual field), only those areas that are functionally related to midline representation are linked to the contralateral hemisphere. This is most clearly seen for the visual areas, where the cortex containing the representation of each midline retinal zone is linked to its counterpart on the contralateral side. A similar arrangement is seen in somatic areas, where the trunk representation is callosally linked, but the peripheral limb areas (hand and foot) are not.

Connections that link the same, or similar, areas on each side are termed homotopic connections. The corpus callosum also interconnects heterogeneous cortical areas on the two sides (heterotopic connections). These may serve to connect functionally similar, but anatomically different, loci in the two hemispheres, and/or to connect functional areas in one hemisphere with regions that are specialized for a unilaterally confined function in the other.

Anterior commissure

The anterior commissure is a compact bundle of myelinated nerve fibres which crosses anterior to the columns of the fornix and is embedded in the lamina terminalis, where it is part of the anterior wall of the third ventricle (Fig. 23.13). In sagittal section it is oval, its long (vertical) diameter is approximately 1.5 mm. Laterally it splits into anterior and posterior bundles. The smaller anterior bundle curves forwards on each side to the anterior perforated substance and olfactory tract. The posterior bundle curves posterolaterally on each side in a deep groove on the anteroinferior aspect of the lentiform complex, and subsequently fans out into the anterior part of the temporal lobe, including the parahippocampal gyrus. Areas thought to be connected via commissural fibres include: the olfactory bulb and anterior olfactory nucleus; the anterior perforated substance, olfactory tubercle and diagonal band of Broca; the prepiriform cortex; the entorhinal area and adjacent parts of the parahippocampal gyrus; part of the amygdaloid complex (especially the nucleus of the lateral olfactory stria); the bed nucleus of the stria terminalis and the nucleus accumbens; the anterior regions of the middle and inferior temporal gyri.

Internal capsule

In horizontal cerebral sections the internal capsule appears as a broad white band, with a lateral concavity, which accommodates the lentiform complex (Fig. 23.27, Fig. 23.28, Fig. 23.29). It has an anterior limb, genu, posterior limb, and retrolenticular (retrolentiform) and sublenticular (sublentiform) parts. Both anterior and posterior limbs are medial to the lentiform complex. The head of the caudate nucleus is medial to the anterior limb, and the thalamus is medial to the posterior limb. Cortical efferent fibres of the internal capsule continue to converge as they descend. Fibres derived from the frontal lobe tend to pass posteromedially, while temporal and occipital fibres pass anterolaterally. Many, but not all, corticofugal fibres pass into the crus cerebri of the ventral midbrain. Here, corticospinal and corticobulbar fibres are located in the middle half of the crus. Frontopontine fibres are located medially, whereas corticopontine fibres from temporal, parietal and occipital cortices are found laterally.

Fig. 23.28 Horizontal section of the brain through the frontal and occipital poles of the cerebral hemispheres. (Figure enhanced by B. Crossman.)

Fig. 23.29 Horizontal section through the internal capsule illustrating its main fibre components.

The anterior limb of the internal capsule contains frontopontine fibres, which arise from the cortex in the frontal lobe. They synapse with cells in the pontine nuclei. Axons of these cells enter the opposite cerebellar hemisphere through the middle cerebellar peduncle. Anterior thalamic radiations interconnect the medial and anterior thalamic nuclei and various hypothalamic nuclei and limbic structures with the frontal cortex.

The genu of the internal capsule is usually regarded as containing corticobulbar fibres, which are mainly derived from area 4 and terminate mostly in the contralateral motor nuclei of cranial nerves. Anterior fibres of the superior thalamic radiation, between the thalamus and cortex, also extend into the genu.

The posterior limb of the internal capsule includes the corticospinal tract. The fibres concerned with the upper limb are anterior. More posterior regions contain fibres representing the trunk and lower limbs. Other descending axons include frontopontine fibres, particularly from areas 4 and 6, and corticorubral fibres, which connect the frontal lobe to the red nucleus. Most of the posterior limb also contains fibres of the superior thalamic radiation (the somaesthetic radiation) ascending to the postcentral gyrus.

The retrolenticular part of the internal capsule contains parietopontine, occipitopontine, and occipitotectal fibres. It also includes the posterior thalamic radiation and the optic radiation, and interconnections between the occipital and parietal lobes and caudal parts of the thalamus, especially the pulvinar.

The optic radiation arises in the lateral geniculate body. It sweeps backwards, intimately related to the superolateral aspect of the inferior horn and the lateral aspect of the posterior horn of the lateral ventricle, from which it is separated by the tapetum.

The sublenticular part of the internal capsule contains temporopontine and some parietopontine fibres, the auditory radiation from the medial geniculate body to the superior temporal and transverse temporal gyri (areas 41 and 42), and a few fibres that connect the thalamus with the temporal lobe and insula. Fibres of the auditory radiation sweep anterolaterally below and behind the lentiform complex to reach the cortex.