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The brain: functional divisions
Physiology
The brain: functional divisions
Primary and secondary vesicles of the developing CNS
Leo Donnelly
Abstract The incompletely separated cerebral hemispheres consist of a thin outer folded cortex of grey matter containing organized neuronal cell bodies and interneurons. Some of the surface convolutions subserve particular sensory or motor functions. Incoming afferent and projected efferent fibres constitute the underlying white matter, which connects different parts of each hemisphere, the hemispheres to each other and (as the corona radiata) to subcortical nuclei, especially components of the deeply-embedded diencephalon and the basal ganglia, and continuing between the latter as the internal capsule to and from the cerebellum and brainstem. Divisions of the diencephalon, the deeper part of the embryonic forebrain, include the epithalamus (pineal gland), the tha lamus (connected extensively with the cortex), the subthalamus and the hypothalamus (involved in the autonomic nervous system, limbic system and neuro-endocrine system). The brainstem, consisting of the midbrain, pons and medulla, allows passage of many ascending and descending nerve fibre tracts between the brain and spinal cord, carrying sensory information from and allowing movement of the limbs and trunk. It is also the site of many of the cranial nerve nuclei, through which the brain innervates the head region. It houses the centres controlling vital aspects related to respiration, cardiovascular function and consciousness levels. The cerebellum also has a cortex of grey matter, tightly convoluted into folia, and containing layered neuronal cell bodies projecting laterally and, as underlying white matter, to a collection of deep nuclei. Fibres run to and from the cerebellar nuclei in a series of peduncles to the midbrain, pons and medulla, and allow the cerebellum to coordinate movement at an unconscious level.
Keywords basal ganglia; hemispheres; physiology
brainstem;
brain
function;
Secondary vesicles
Derivative(s)
Prosencephalon (forebrain)
Telencephalon Diencephalon
Cerebral hemispheres Thalamus (etc.)
Mesencephalon (midbrain)
Mesencephalon
Midbrain
Rhombencephalon (hindbrain)
Metencephalon Myelencephalon
Pons, cerebellum Medulla oblongata
Table 1
the alar plate have mainly sensory functions; those in the basal plate are mainly motor.
Cerebral hemispheres The human brain is dominated by the telencephalon, which expands to cover the diencephalon as the cerebral hemispheres. Their outer mantle of cortical grey matter (rich in neuronal cell bodies) varies between 1.5 and 4.5 mm in thickness, and devel ops an increased surface area by virtue of folds (gyri) separated by grooves (sulci), in the walls of which about 70% of the cor tex is hidden. The cortex tends to be thicker on the crest of a gyrus than in the depths of a sulcus. It is technically very dif ficult to count the enormous number of cortical neuronal cell bodies, and estimates vary between 2.6 × 109 and 1.6 × 1010. They project into and receive connections from the interior of the hemisphere, and many of these fibres are sheathed in fatty, insu lating myelin, conferring a paler coloration (the white matter). Embedded within the white matter are the basal ganglia (cau date nucleus, putamen, globus pallidus, etc.) and the fibres pass around a system of ventricles containing cerebrospinal fluid. The cortex also contains 5.0 × 1011 ancillary neuroglial cells of vari ous types, and dense capillary beds. Microscopically, the cytoarchitecture of the cortex is found to have both a laminar and a columnar organization. Phylogenetic ally old parts of the cortex – the paleocortex of the uncus (con cerned with olfaction and some limbic areas) and the archicortex of the hippocampus (concerned with memory) – have three or more laminae, while in the neocortex, which covers the remain ing 90% of the brain, six cellular laminae (numbered from the outside in) can usually be discerned (Figure 1), especially in association areas. The three principal neuronal cell morphologies found in these layers are pyramidal, spiny stellate and smooth stellate cells. The large pyramidal cells vary in height from 20 (in laminae II and III) to 60 μm (in lamina V), but also include the giant cells of Betz (80–100 μm) in the primary motor cortex. Their cell bodies are conical in shape with a single apical dendrite, which usually extends to lamina I, and several basal dendrites which extend laterally within the same lamina as the cell body. These den drites branch freely and are decorated with spines. The axons of all pyramidal cells give rise to recurrent branches before leaving the cortex, which may excite neighbouring pyramidal cells (all
cerebral
The CNS develops as a groove in the embryonic ectoderm, the edges of which fold over to enclose a neural tube during the fourth week of development. The closed forward or rostral end of this tube differentially expands into three primary vesicles and, by the seventh week of development, five secondary ves icles (Table 1). By convention, the midbrain, pons and medulla are known collectively as the brainstem. There is also an early delineation between dorsal and ventral cell groupings (the alar and basal plates, respectively) in the developing spinal cord and neighbouring (caudal) parts of the brain. Neurons developing in
Leo Donnelly, PhD, is Anatomy Lecturer in Phase 1 Medicine at the University of Durham, Queen’s campus. He obtained his PhD from the University of London, London, UK.
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Physiology
as anatomical landmarks. The sulci indent the surface of the hemispheres and are distinct from the much deeper longitudinal and lateral fissures. The hemispheres are separated by the lon gitudinal fissure, which accommodates a crescentic indentation of the dura mater – the falx cerebri – until it reaches the corpus callosum. Each hemisphere is also divided into four superficial lobes by the lateral fissure, the relatively constant and deep central sulcus, and two imaginary lines: an extrapolation of the lateral fissure until it meets a line extending from the parietooccipital sulcus as it emerges from the medial surface onto the superior margin of the hemisphere (about 4 cm from the occipi tal pole), to the preoccipital notch on the inferior margin of the hemisphere. The lobes are named with regard to the bones of the skull that they more-or-less underlie: frontal, parietal, occipital and temporal. In addition, the lips (opercula) of the lateral fissure can be retracted to expose a fifth lobe, the insula, which remains bound to the underlying corpus striatum during development. The lateral fissure is formed by expansion of the surrounding cortex during development.
Laminar arrangement of neocortex I
II + +
III SpS IV
SmS +
+
P2
V
P1
P3
Frontal lobe: this lobe occupies the volume anterior to the cen tral sulcus and, on the medial surface of the brain, an imaginary line drawn between the superior end of the central sulcus and the corpus callosum. Anterior to the central sulcus is the often incomplete precentral sulcus, delineating the precentral gyrus (Brodmann’s area 4 – see below) which correlates functionally with the primary motor cortex. Within this portion of the cortex, afferent fibres project in a somatotopic fashion (often depicted as a distorted and inverted ‘motor homunculus’ – the head area occurring just above the lateral fissure and the lower limb on the medial surface of the hemisphere). The area of premotor cor tex devoted to a particular part of the body is proportional to the number of neuronal cell bodies and efferent fibres associ ated with the body part, and therefore the degree of precision involved in its movement. Stimulation of a point on the primary motor cortex results in contraction of particular muscle groups on the contralateral side of the body. The German anatomist Korbinian Brodmann published a cytoarchitectural map of 52 numbered areas in 1909, which has been superseded by functional studies. There remains, however, remarkably good correspondence between his areas and func tional maps, and his numbering system is still in common use for descriptive purposes (Figure 2). The premotor cortex occupies an area immediately anterior to and six times larger than the primary motor cortex, correspond ing to that part of Brodmann’s area 6 on the lateral surface of the frontal lobe. It receives input from other parts of the frontal lobe as well as a rich sensory input from Brodmann’s area 7 of the parietal lobe. It is especially active in response to visual or somatic sensory cues (e.g. reaching for an object in full view, or identifying an object by touch alone). The premotor cortex is usually active bilaterally, which may be due to commissural transfer of planned motor action through the corpus callosum. The premotor cortex has a major projection to brainstem nuclei that give rise to reticulospinal tracts. One of its major functions seems to be bilateral postural fixation (e.g. stabilization of the hips during walking). The supplementary motor area occupies a neighbouring part of Brodmann’s area 6 on the medial surface of the frontal lobe. In
VI TC
A thalamocortical afferent (TC), three pyramidal cells (P1–3), and a spiny (SpS) and a smooth (SmS) stellate cell are shown
Figure 1
yramidal cells are excitatory, using glutamate or the closelyp related aspartate as a neurotransmitter). Spiny stellate cells also have spiny dendrites and are usu ally excitatory. Their cell bodies are restricted to lamina IV and receive most of the afferent input from the thalamus and from other areas of the cortex, and form glutamatergic synapses on pyramidal cells. Smooth stellate cells have dendrites lacking spines and their cell bodies are also restricted to lamina IV, where they receive some of the recurrent collateral branches of pyram idal cells and form inhibitory γ-aminobutyric acid (GABA)ergic synapses on other pyramidal cells. Cells of the cortex are also arranged in 200–500 μm diameter, modality-specific columns, extending radially through all lam inae. Such columns, also known as modules, are composed of about 100 mini-columns (radial chains of neurons) and are the functional units of the cortex; they may be activated by specific afferents, whether thalamocortical, association or commissural (see below). Neocortical modules are established during fetal development, but establish synaptic connections postnatally and in response to external sensory stimuli (the so-called early crit ical period). The cortical gyri and sulci are somewhat variable, even between the hemispheres, but some are constant enough to serve
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Parietal lobe: this lobe includes the somatic sensory cortex, which occupies the entire postcentral gyrus (Brodmann’s areas 3, 1 and 2, rostral to caudal). It receives afferents from the ventral posterior nucleus of the thalamus, which is the site of termination of the spinothalamic tracts, trigeminothalamic tract and medial lemniscus. Somatotopic representation of body parts is not dis similar to that of the primary motor cortex, but any homunculus should be considered schematic only, because there is a great deal of overlap in sensory representation between body regions. The rostral area 3 is divided into a small strip (3a) deep in the central sulcus, which receives information relayed from muscle spindles, and a larger, granular strip (3b), which receives infor mation relayed from skin, and is regarded as the true primary somatosensory cortex (S1). Some modules in the more superficial area 1 receive input from a single digit. They are capable of a phe nomenon known as feature extraction (i.e. some are rapidly and some are slowly adapting, some respond to skin being stroked in a particular direction and some respond only to noxious stimuli). Modules in the more caudal area 2 receive input from multidigit fields from muscles and joint capsules as well as skin. Caudal to the somatosensory cortex is the sensory association cortex, which is divided into a superior and an inferior parietal lobule by an intraparietal sulcus. The superior lobule is thought to be responsible for conscious awareness of the contralateral half of the body and interpretation of general sensory input. Lesions of this part of the cortex result in impairment of under standing and interpretation of sensory information, and may result in neglect of the contralateral side of the body. The inferior lobule interfaces between the somatosensory cortex, the visual association cortex of the occipital lobe and the auditory associa tion cortex of the temporal lobe. In the dominant (usually left) hemisphere it is associated with language functions.
Cytoarchitectural areas of Brodmann Lateral surface 6
8
4
9
5
3 1
7 2 40
46 44 42
45
10
19 39
41
22
47
18 21
11
17
37
38 20
Medial surface
3 6
8 9
4
1 2 7
5 24
32
31
19
23
18 17
10 12 11
25
18 34
36 28
38
37
19
20
4, primary motor cortex; medial 6, supplementary motor area; lateral 6, premotor cortex; 3, 1 and 2, (primary) somatic sensory cortex; 40, secondary somatic sensory cortex; 17, primary visual cortex; 18 and 19, visual association cortex; 41 and 42, primary auditory cortex; 22, auditory association cortex
Occipital lobe: the occipital lobe lies caudal to the parietal and temporal lobes. Its medial surface is marked by the deep parietooccipital sulcus and the calcarine sulcus, the adjacent cortex of which constitutes the primary visual cortex (Brodmann’s area 17). It receives fibres from the lateral geniculate nucleus of the thalamus via the optic radiation (part of the internal capsule). The lateral (temporal) half of each visual field is represented in the primary visual cortex of the contralateral hemisphere, the medial (nasal) half in that of the ipsilateral hemisphere. The rep resentation is also inverted so that the upper half of the visual field is represented in cortex below the calcarine sulcus and the lower half above the sulcus. Lesions result in blindness in the corresponding part of the visual field. The remainder of the lobe constitutes the visual association cortex, which is concerned with interpretation of visual images. Lesions result in difficulties in visual interpretation and recognition.
Figure 2
contrast to the responsiveness of the premotor cortex to external cues, the supplementary motor area seems to respond to internal cues, especially intentions to make voluntary movements (even if the movement is not carried out). Its principal function seems to be to preprogramme sequences of movements that are already built into a motor memory. It functions in conjunction with ‘direct’ five- or ‘indirect’ seven-neuron motor circuits through individual basal ganglia and which project to the primary motor cortex as well as to the corticospinal tracts. Lesions are associated with contralateral inability to initiate movements (akinesia). Rostral to the premotor cortex in the middle frontal gyrus is the frontal eye field (the lower part of Brodmann’s area 8), which controls voluntary conjugate saccadic movements of the eyes. A unilateral lesion will cause conjugate deviation of the eyes towards the side of the lesion. The inferior frontal gyrus of the dominant hemisphere (usually the left) contains the (Broca’s) motor speech area (Brodmann’s areas 44 and 45), which has important connections with parts of the ipsilateral temporal, parietal and occipital lobes concerned with language function.
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Temporal lobe: the lateral surface of the temporal lobe is com posed of three gyri – superior, middle and inferior – running roughly parallel with the lateral fissure. Its superior surface, hid den within the fissure, is marked by small transverse temporal gyri (Heschl’s convolutions), which mark the location of the primary auditory cortex (Brodmann’s areas 41 and 42), respon sible for the conscious perception of sound. It receives input from the ascending acoustic projection, which undergoes partial decussation in the brainstem en route to the medial geniculate 218
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Physiology
nucleus of the thalamus. Cortical input from the medial genicu late nucleus is arranged as a bilateral ‘tonotopical’ representation of the cochlear duct. Unilateral lesions of the primary auditory cortex will therefore cause partial deafness in both ears. Further processing and interpretation of auditory information occurs in the surrounding auditory association cortex (Brodmann’s area 22), known as Wernicke’s area in the dominant hemisphere. It allows for understanding of the spoken word, and connects with other language areas of the brain. The location of the cortical representation of the vestibular (balance) system is uncertain, but may be in the superior tem poral gyrus rostral to the primary auditory cortex, or in the infe rior parietal lobule. Inferomedially, the temporal lobe curls inward to form the hippocampus. It lies in the floor of the inferior horn of the lateral ventricle, deep to the parahippocampal gyrus, and forms part of the limbic system (see below). As such, its functions relate to short-term memory and the emotional aspects of behaviour. Lying close to the anterior end of the hippocampus is the amyg dala – a mass of subcortical grey matter that also forms part of the limbic system. The amygdala and adjacent parts of the infero medial temporal cortex receive fibres from the olfactory tract, and are associated with the conscious appreciation of smells.
Association fibres within the right cerebral hemisphere Arcuate fasciculus Cingulum Corpus callosum Superior longitudinal fasciculus Short association fibres
Uncinate fasciculus
The insula is one of the cortical centres for pain, and is also involved in involuntary activities such as the control of viscera by the autonomic nervous system. Cortical areas for the special visceral sensations of taste and smell also extend onto the insula. It overlies the lentiform nucleus, a component of the corpus stria tum, and is separated from it by two layers of white matter (the external and extreme capsules) and an intervening layer of grey matter (the claustrum). Efferent (outgoing) fibres from all parts of the cortex derive from pyramidal cells and are excitatory (Figure 3). They can be classified as: • Association fibres (linking parts of the same hemisphere) – these may be further divided into short-association (connect ing one gyrus to another within a lobe, also known as U-fibres) or long-association fibres (connecting one lobe with another). Examples of the latter include: superior longitudinal fasciculus (between the frontal and occipital lobes), and its subsidiary, the arcuate fasciculus (between the frontal lobe and occipitotem poral cortex, carrying fibres important for language function); inferior longitudinal fasciculus (between the occipital and tem poral lobes, contributing to visual recognition); uncinate fascicu lus (between the frontal and anterior temporal lobes, important in the regulation of behaviour); cingulum (deep to the cingulate gyrus, connecting the frontal and parietal lobes with the parahip pocampal and adjacent temporal gyri) • Commissural fibres (linking corresponding parts of the two hemispheres) – these include the massive corpus callosum, and also the anterior and posterior commissures, the habenular com missure and the commissure of the fornix. Fibres running in the body of the corpus callosum may pass laterally and superiorly to intersect with a fan-like radiation of fibres running to and from the cortex (the corona radiata). Other fibres pass laterally and in feriorly to the temporal and occipital lobes as the tapetum. Fibres passing in the posterior splenium of the corpus callosum project to the medial wall of each occipital lobe, forming the occipital
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Anterior commisure Inferior longitudinal fasciculus Figure 3
forceps (major), while fibres passing in the anterior genu of the corpus callosum project to the medial wall of each frontal lobe, forming the frontal forceps (minor). • Projection fibres – these run to the subcortical nuclei, the brainstem and spinal cord. Those from the primary sensory and motor cortices form the largest input to the basal ganglia. Cortical afferent (incoming) fibres are derived from: • Long- and short-association fibres (described above). • Commissural fibres (described above). • Specific thalamocortical fibres from a particular or association nucleus of the thalamus (e.g. from the ventral posterior thalamic nucleus to the somatic sensory cortex, or dorsomedial thalamic nucleus to the prefrontal cortex). • Non-specific thalamocortical fibres from the intralaminar nuclei. • Cholinergic and aminergic fibres from the basal forebrain, hypothalamus and brainstem. Basal ganglia: the term basal ganglia (Figure 4) designates those parts (actually nuclei) of the basal telencephalon and midbrain involved in the control of movement. They include the: • striatum (caudate nucleus, putamen of the lentiform nucleus and the nucleus accumbens) • pallidum (globus pallidus of the lentiform nucleus; its lateral and medial parts, including the latter’s reticular extension into the midbrain) • subthalamic nucleus • compact part of the substantia nigra 219
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The thalamus is the largest component of the diencephalon and is composed of numerous nuclei, including those with con nections with associative and limbic areas of the cortex, those that receive input from the cerebellum and basal ganglia and project to the motor regions of the frontal lobe, and those that transmit general and special sensory information to correspond ing parts of the sensory cortices. The lateral ventricles of the cerebral hemispheres drain into the third ventricle, which lies in the midline between the thalami. The epithalamus consists principally of the pineal gland (an endocrine organ that secretes melatonin and is involved with cir cadian rhythm and regulation of the onset of puberty) and the habenular nuclei (which connect with the limbic system). The subthalamus lies inferior to the thalamus and dorsolateral to the hypothalamus. It contains two notable cell groups: the subthalamic nucleus (connects to the globus pallidus and sub stantia nigra and is involved with the control of movement), and the zona incerta (a rostral extension of the brainstem reticular formation). The hypothalamus has important connections with the lim bic system, a controlling influence on autonomic nervous system activity and a role in neuroendocrine function.
Basal ganglia and some connections
Caudate
Thalamus Putamen
VL
Globus pallidus
Subthalamic nucleus
Corticospinal tract
Cerebellum The cerebellum coordinates movement by maintenance of equi librium (the archicerebellum, the flocculonodular lobe and fas tigial nuclei), posture and muscle tone (the paleocerebellum, the midline vermis, paravermis and the globose and emboliform nuclei) at an unconscious level. The neocerebellum (the remain der of each cerebellar hemisphere and the dentate nucleus) is
Connections shown are with the ventral lateral (VL) nucleus of the thalamus, the neurons of which project to the cortex
Figure 4
Four basic circuits are known to occur from the cerebral cor tex, through the basal ganglia and back to the cortex, by a direct or indirect route: a motor loop is concerned with learned move ments; a cognitive loop with motor intentions; a limbic loop with emotional aspects of movement and an oculomotor loop with voluntary saccades.
Sagittal section of brainstem Tectal plate PAG Aqueduct Central grey matter
Limbic system: this system is composed of the ‘limbic lobe’ (the parahippocampal and cingulate gyri and the septal area), the hip pocampal formation (the subiculum, hippocampus and dentate gyrus), and the amygdala amongst others. Declarative memory (i.e. of new facts and events) may occur as modifications of syn apses within the hippocampus. Declarative memory requires the circuit of Papez (including the subiculum, fornix, mamil lary body, anterior thalamic nuclei and cingulate and parahippo campal gyri) to be intact in at least one hemisphere. However, the recall of memories does not seem to require intact hippocampal connections, and are probably stored as synaptic modifications in the cortex.
Tegmentum Fourth ventricle Pons
Emerging cerebrospinal fluid Pyramid Central canal Spinal cord
Diencephalon The diencephalon is continuous with the rostral midbrain and lies between it and the cerebral hemisphere, by which it is almost completely surrounded. It comprises, from superior to inferior, the epithalamus, thalamus, subthalamus and hypothalamus.
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PAG, periaqueductal grey
Figure 5
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concerned with muscular coordination, including trajectory, speed and force of movements. The cerebellar cortex consists of highly convoluted folia, which cover the white matter. Within the white matter are embedded the cerebellar nuclei, which are the source of efferent fibres to the brainstem by way of three pairs of cerebellar peduncles.
The tectum (roof) of the midbrain is formed by four col liculi – the paired superior colliculi are associated with the visual system, and the inferior colliculi with the auditory system. The intermediate region of the brainstem is known as the tegmentum, which contains the reticular formation, the ascending sensory pathways carrying general sensory information from the trunk and limbs (especially the posterior column-medial lemniscal pathways), and the descending motor corticospinal tracts – the latter two decussate in the medulla oblongata. ◆
Brainstem The third ventricle drains into an aqueduct in the midbrain, which opens into the fourth ventricle dorsal to the pons and upper medulla oblongata. From the fourth ventricle cerebro spinal fluid emerges from three apertures into the subarachnoid space. A negligible amount moves into the central canal of the spinal cord. The brainstem houses the nuclei of cranial nerves III to XII, all of which emerge anteriorly except the trochlear nerve (cranial nerve IV) (Figure 5).
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Further reading Crossman AR, Neary D. Neuroanatomy, 3rd edn. Edinburgh: Churchill Livingstone, 2005. Fitzgerald MJT, Gregory G, Mtui E. Clinical neuroanatomy and neuroscience, 5th edn. Philadelphia: Saunders, 2007.
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The brain: functional divisions
Primary and secondary vesicles of the developing CNS
Leo Donnelly
Abstract The incompletely separated cerebral hemispheres consist of a thin outer folded cortex of grey matter containing organized neuronal cell bodies and interneurons. Some of the surface convolutions subserve particular sensory or motor functions. Incoming afferent and projected efferent fibres constitute the underlying white matter, which connects different parts of each hemisphere, the hemispheres to each other and (as the corona radiata) to subcortical nuclei, especially components of the deeply-embedded diencephalon and the basal ganglia, and continuing between the latter as the internal capsule to and from the cerebellum and brainstem. Divisions of the diencephalon, the deeper part of the embryonic forebrain, include the epithalamus (pineal gland), the tha lamus (connected extensively with the cortex), the subthalamus and the hypothalamus (involved in the autonomic nervous system, limbic system and neuro-endocrine system). The brainstem, consisting of the midbrain, pons and medulla, allows passage of many ascending and descending nerve fibre tracts between the brain and spinal cord, carrying sensory information from and allowing movement of the limbs and trunk. It is also the site of many of the cranial nerve nuclei, through which the brain innervates the head region. It houses the centres controlling vital aspects related to respiration, cardiovascular function and consciousness levels. The cerebellum also has a cortex of grey matter, tightly convoluted into folia, and containing layered neuronal cell bodies projecting laterally and, as underlying white matter, to a collection of deep nuclei. Fibres run to and from the cerebellar nuclei in a series of peduncles to the midbrain, pons and medulla, and allow the cerebellum to coordinate movement at an unconscious level.
Keywords basal ganglia; hemispheres; physiology
brainstem;
brain
function;
Secondary vesicles
Derivative(s)
Prosencephalon (forebrain)
Telencephalon Diencephalon
Cerebral hemispheres Thalamus (etc.)
Mesencephalon (midbrain)
Mesencephalon
Midbrain
Rhombencephalon (hindbrain)
Metencephalon Myelencephalon
Pons, cerebellum Medulla oblongata
Table 1
the alar plate have mainly sensory functions; those in the basal plate are mainly motor.
Cerebral hemispheres The human brain is dominated by the telencephalon, which expands to cover the diencephalon as the cerebral hemispheres. Their outer mantle of cortical grey matter (rich in neuronal cell bodies) varies between 1.5 and 4.5 mm in thickness, and devel ops an increased surface area by virtue of folds (gyri) separated by grooves (sulci), in the walls of which about 70% of the cor tex is hidden. The cortex tends to be thicker on the crest of a gyrus than in the depths of a sulcus. It is technically very dif ficult to count the enormous number of cortical neuronal cell bodies, and estimates vary between 2.6 × 109 and 1.6 × 1010. They project into and receive connections from the interior of the hemisphere, and many of these fibres are sheathed in fatty, insu lating myelin, conferring a paler coloration (the white matter). Embedded within the white matter are the basal ganglia (cau date nucleus, putamen, globus pallidus, etc.) and the fibres pass around a system of ventricles containing cerebrospinal fluid. The cortex also contains 5.0 × 1011 ancillary neuroglial cells of vari ous types, and dense capillary beds. Microscopically, the cytoarchitecture of the cortex is found to have both a laminar and a columnar organization. Phylogenetic ally old parts of the cortex – the paleocortex of the uncus (con cerned with olfaction and some limbic areas) and the archicortex of the hippocampus (concerned with memory) – have three or more laminae, while in the neocortex, which covers the remain ing 90% of the brain, six cellular laminae (numbered from the outside in) can usually be discerned (Figure 1), especially in association areas. The three principal neuronal cell morphologies found in these layers are pyramidal, spiny stellate and smooth stellate cells. The large pyramidal cells vary in height from 20 (in laminae II and III) to 60 μm (in lamina V), but also include the giant cells of Betz (80–100 μm) in the primary motor cortex. Their cell bodies are conical in shape with a single apical dendrite, which usually extends to lamina I, and several basal dendrites which extend laterally within the same lamina as the cell body. These den drites branch freely and are decorated with spines. The axons of all pyramidal cells give rise to recurrent branches before leaving the cortex, which may excite neighbouring pyramidal cells (all
cerebral
The CNS develops as a groove in the embryonic ectoderm, the edges of which fold over to enclose a neural tube during the fourth week of development. The closed forward or rostral end of this tube differentially expands into three primary vesicles and, by the seventh week of development, five secondary ves icles (Table 1). By convention, the midbrain, pons and medulla are known collectively as the brainstem. There is also an early delineation between dorsal and ventral cell groupings (the alar and basal plates, respectively) in the developing spinal cord and neighbouring (caudal) parts of the brain. Neurons developing in
Leo Donnelly, PhD, is Anatomy Lecturer in Phase 1 Medicine at the University of Durham, Queen’s campus. He obtained his PhD from the University of London, London, UK.
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Physiology
as anatomical landmarks. The sulci indent the surface of the hemispheres and are distinct from the much deeper longitudinal and lateral fissures. The hemispheres are separated by the lon gitudinal fissure, which accommodates a crescentic indentation of the dura mater – the falx cerebri – until it reaches the corpus callosum. Each hemisphere is also divided into four superficial lobes by the lateral fissure, the relatively constant and deep central sulcus, and two imaginary lines: an extrapolation of the lateral fissure until it meets a line extending from the parietooccipital sulcus as it emerges from the medial surface onto the superior margin of the hemisphere (about 4 cm from the occipi tal pole), to the preoccipital notch on the inferior margin of the hemisphere. The lobes are named with regard to the bones of the skull that they more-or-less underlie: frontal, parietal, occipital and temporal. In addition, the lips (opercula) of the lateral fissure can be retracted to expose a fifth lobe, the insula, which remains bound to the underlying corpus striatum during development. The lateral fissure is formed by expansion of the surrounding cortex during development.
Laminar arrangement of neocortex I
II + +
III SpS IV
SmS +
+
P2
V
P1
P3
Frontal lobe: this lobe occupies the volume anterior to the cen tral sulcus and, on the medial surface of the brain, an imaginary line drawn between the superior end of the central sulcus and the corpus callosum. Anterior to the central sulcus is the often incomplete precentral sulcus, delineating the precentral gyrus (Brodmann’s area 4 – see below) which correlates functionally with the primary motor cortex. Within this portion of the cortex, afferent fibres project in a somatotopic fashion (often depicted as a distorted and inverted ‘motor homunculus’ – the head area occurring just above the lateral fissure and the lower limb on the medial surface of the hemisphere). The area of premotor cor tex devoted to a particular part of the body is proportional to the number of neuronal cell bodies and efferent fibres associ ated with the body part, and therefore the degree of precision involved in its movement. Stimulation of a point on the primary motor cortex results in contraction of particular muscle groups on the contralateral side of the body. The German anatomist Korbinian Brodmann published a cytoarchitectural map of 52 numbered areas in 1909, which has been superseded by functional studies. There remains, however, remarkably good correspondence between his areas and func tional maps, and his numbering system is still in common use for descriptive purposes (Figure 2). The premotor cortex occupies an area immediately anterior to and six times larger than the primary motor cortex, correspond ing to that part of Brodmann’s area 6 on the lateral surface of the frontal lobe. It receives input from other parts of the frontal lobe as well as a rich sensory input from Brodmann’s area 7 of the parietal lobe. It is especially active in response to visual or somatic sensory cues (e.g. reaching for an object in full view, or identifying an object by touch alone). The premotor cortex is usually active bilaterally, which may be due to commissural transfer of planned motor action through the corpus callosum. The premotor cortex has a major projection to brainstem nuclei that give rise to reticulospinal tracts. One of its major functions seems to be bilateral postural fixation (e.g. stabilization of the hips during walking). The supplementary motor area occupies a neighbouring part of Brodmann’s area 6 on the medial surface of the frontal lobe. In
VI TC
A thalamocortical afferent (TC), three pyramidal cells (P1–3), and a spiny (SpS) and a smooth (SmS) stellate cell are shown
Figure 1
yramidal cells are excitatory, using glutamate or the closelyp related aspartate as a neurotransmitter). Spiny stellate cells also have spiny dendrites and are usu ally excitatory. Their cell bodies are restricted to lamina IV and receive most of the afferent input from the thalamus and from other areas of the cortex, and form glutamatergic synapses on pyramidal cells. Smooth stellate cells have dendrites lacking spines and their cell bodies are also restricted to lamina IV, where they receive some of the recurrent collateral branches of pyram idal cells and form inhibitory γ-aminobutyric acid (GABA)ergic synapses on other pyramidal cells. Cells of the cortex are also arranged in 200–500 μm diameter, modality-specific columns, extending radially through all lam inae. Such columns, also known as modules, are composed of about 100 mini-columns (radial chains of neurons) and are the functional units of the cortex; they may be activated by specific afferents, whether thalamocortical, association or commissural (see below). Neocortical modules are established during fetal development, but establish synaptic connections postnatally and in response to external sensory stimuli (the so-called early crit ical period). The cortical gyri and sulci are somewhat variable, even between the hemispheres, but some are constant enough to serve
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Parietal lobe: this lobe includes the somatic sensory cortex, which occupies the entire postcentral gyrus (Brodmann’s areas 3, 1 and 2, rostral to caudal). It receives afferents from the ventral posterior nucleus of the thalamus, which is the site of termination of the spinothalamic tracts, trigeminothalamic tract and medial lemniscus. Somatotopic representation of body parts is not dis similar to that of the primary motor cortex, but any homunculus should be considered schematic only, because there is a great deal of overlap in sensory representation between body regions. The rostral area 3 is divided into a small strip (3a) deep in the central sulcus, which receives information relayed from muscle spindles, and a larger, granular strip (3b), which receives infor mation relayed from skin, and is regarded as the true primary somatosensory cortex (S1). Some modules in the more superficial area 1 receive input from a single digit. They are capable of a phe nomenon known as feature extraction (i.e. some are rapidly and some are slowly adapting, some respond to skin being stroked in a particular direction and some respond only to noxious stimuli). Modules in the more caudal area 2 receive input from multidigit fields from muscles and joint capsules as well as skin. Caudal to the somatosensory cortex is the sensory association cortex, which is divided into a superior and an inferior parietal lobule by an intraparietal sulcus. The superior lobule is thought to be responsible for conscious awareness of the contralateral half of the body and interpretation of general sensory input. Lesions of this part of the cortex result in impairment of under standing and interpretation of sensory information, and may result in neglect of the contralateral side of the body. The inferior lobule interfaces between the somatosensory cortex, the visual association cortex of the occipital lobe and the auditory associa tion cortex of the temporal lobe. In the dominant (usually left) hemisphere it is associated with language functions.
Cytoarchitectural areas of Brodmann Lateral surface 6
8
4
9
5
3 1
7 2 40
46 44 42
45
10
19 39
41
22
47
18 21
11
17
37
38 20
Medial surface
3 6
8 9
4
1 2 7
5 24
32
31
19
23
18 17
10 12 11
25
18 34
36 28
38
37
19
20
4, primary motor cortex; medial 6, supplementary motor area; lateral 6, premotor cortex; 3, 1 and 2, (primary) somatic sensory cortex; 40, secondary somatic sensory cortex; 17, primary visual cortex; 18 and 19, visual association cortex; 41 and 42, primary auditory cortex; 22, auditory association cortex
Occipital lobe: the occipital lobe lies caudal to the parietal and temporal lobes. Its medial surface is marked by the deep parietooccipital sulcus and the calcarine sulcus, the adjacent cortex of which constitutes the primary visual cortex (Brodmann’s area 17). It receives fibres from the lateral geniculate nucleus of the thalamus via the optic radiation (part of the internal capsule). The lateral (temporal) half of each visual field is represented in the primary visual cortex of the contralateral hemisphere, the medial (nasal) half in that of the ipsilateral hemisphere. The rep resentation is also inverted so that the upper half of the visual field is represented in cortex below the calcarine sulcus and the lower half above the sulcus. Lesions result in blindness in the corresponding part of the visual field. The remainder of the lobe constitutes the visual association cortex, which is concerned with interpretation of visual images. Lesions result in difficulties in visual interpretation and recognition.
Figure 2
contrast to the responsiveness of the premotor cortex to external cues, the supplementary motor area seems to respond to internal cues, especially intentions to make voluntary movements (even if the movement is not carried out). Its principal function seems to be to preprogramme sequences of movements that are already built into a motor memory. It functions in conjunction with ‘direct’ five- or ‘indirect’ seven-neuron motor circuits through individual basal ganglia and which project to the primary motor cortex as well as to the corticospinal tracts. Lesions are associated with contralateral inability to initiate movements (akinesia). Rostral to the premotor cortex in the middle frontal gyrus is the frontal eye field (the lower part of Brodmann’s area 8), which controls voluntary conjugate saccadic movements of the eyes. A unilateral lesion will cause conjugate deviation of the eyes towards the side of the lesion. The inferior frontal gyrus of the dominant hemisphere (usually the left) contains the (Broca’s) motor speech area (Brodmann’s areas 44 and 45), which has important connections with parts of the ipsilateral temporal, parietal and occipital lobes concerned with language function.
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Temporal lobe: the lateral surface of the temporal lobe is com posed of three gyri – superior, middle and inferior – running roughly parallel with the lateral fissure. Its superior surface, hid den within the fissure, is marked by small transverse temporal gyri (Heschl’s convolutions), which mark the location of the primary auditory cortex (Brodmann’s areas 41 and 42), respon sible for the conscious perception of sound. It receives input from the ascending acoustic projection, which undergoes partial decussation in the brainstem en route to the medial geniculate 218
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nucleus of the thalamus. Cortical input from the medial genicu late nucleus is arranged as a bilateral ‘tonotopical’ representation of the cochlear duct. Unilateral lesions of the primary auditory cortex will therefore cause partial deafness in both ears. Further processing and interpretation of auditory information occurs in the surrounding auditory association cortex (Brodmann’s area 22), known as Wernicke’s area in the dominant hemisphere. It allows for understanding of the spoken word, and connects with other language areas of the brain. The location of the cortical representation of the vestibular (balance) system is uncertain, but may be in the superior tem poral gyrus rostral to the primary auditory cortex, or in the infe rior parietal lobule. Inferomedially, the temporal lobe curls inward to form the hippocampus. It lies in the floor of the inferior horn of the lateral ventricle, deep to the parahippocampal gyrus, and forms part of the limbic system (see below). As such, its functions relate to short-term memory and the emotional aspects of behaviour. Lying close to the anterior end of the hippocampus is the amyg dala – a mass of subcortical grey matter that also forms part of the limbic system. The amygdala and adjacent parts of the infero medial temporal cortex receive fibres from the olfactory tract, and are associated with the conscious appreciation of smells.
Association fibres within the right cerebral hemisphere Arcuate fasciculus Cingulum Corpus callosum Superior longitudinal fasciculus Short association fibres
Uncinate fasciculus
The insula is one of the cortical centres for pain, and is also involved in involuntary activities such as the control of viscera by the autonomic nervous system. Cortical areas for the special visceral sensations of taste and smell also extend onto the insula. It overlies the lentiform nucleus, a component of the corpus stria tum, and is separated from it by two layers of white matter (the external and extreme capsules) and an intervening layer of grey matter (the claustrum). Efferent (outgoing) fibres from all parts of the cortex derive from pyramidal cells and are excitatory (Figure 3). They can be classified as: • Association fibres (linking parts of the same hemisphere) – these may be further divided into short-association (connect ing one gyrus to another within a lobe, also known as U-fibres) or long-association fibres (connecting one lobe with another). Examples of the latter include: superior longitudinal fasciculus (between the frontal and occipital lobes), and its subsidiary, the arcuate fasciculus (between the frontal lobe and occipitotem poral cortex, carrying fibres important for language function); inferior longitudinal fasciculus (between the occipital and tem poral lobes, contributing to visual recognition); uncinate fascicu lus (between the frontal and anterior temporal lobes, important in the regulation of behaviour); cingulum (deep to the cingulate gyrus, connecting the frontal and parietal lobes with the parahip pocampal and adjacent temporal gyri) • Commissural fibres (linking corresponding parts of the two hemispheres) – these include the massive corpus callosum, and also the anterior and posterior commissures, the habenular com missure and the commissure of the fornix. Fibres running in the body of the corpus callosum may pass laterally and superiorly to intersect with a fan-like radiation of fibres running to and from the cortex (the corona radiata). Other fibres pass laterally and in feriorly to the temporal and occipital lobes as the tapetum. Fibres passing in the posterior splenium of the corpus callosum project to the medial wall of each occipital lobe, forming the occipital
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Anterior commisure Inferior longitudinal fasciculus Figure 3
forceps (major), while fibres passing in the anterior genu of the corpus callosum project to the medial wall of each frontal lobe, forming the frontal forceps (minor). • Projection fibres – these run to the subcortical nuclei, the brainstem and spinal cord. Those from the primary sensory and motor cortices form the largest input to the basal ganglia. Cortical afferent (incoming) fibres are derived from: • Long- and short-association fibres (described above). • Commissural fibres (described above). • Specific thalamocortical fibres from a particular or association nucleus of the thalamus (e.g. from the ventral posterior thalamic nucleus to the somatic sensory cortex, or dorsomedial thalamic nucleus to the prefrontal cortex). • Non-specific thalamocortical fibres from the intralaminar nuclei. • Cholinergic and aminergic fibres from the basal forebrain, hypothalamus and brainstem. Basal ganglia: the term basal ganglia (Figure 4) designates those parts (actually nuclei) of the basal telencephalon and midbrain involved in the control of movement. They include the: • striatum (caudate nucleus, putamen of the lentiform nucleus and the nucleus accumbens) • pallidum (globus pallidus of the lentiform nucleus; its lateral and medial parts, including the latter’s reticular extension into the midbrain) • subthalamic nucleus • compact part of the substantia nigra 219
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The thalamus is the largest component of the diencephalon and is composed of numerous nuclei, including those with con nections with associative and limbic areas of the cortex, those that receive input from the cerebellum and basal ganglia and project to the motor regions of the frontal lobe, and those that transmit general and special sensory information to correspond ing parts of the sensory cortices. The lateral ventricles of the cerebral hemispheres drain into the third ventricle, which lies in the midline between the thalami. The epithalamus consists principally of the pineal gland (an endocrine organ that secretes melatonin and is involved with cir cadian rhythm and regulation of the onset of puberty) and the habenular nuclei (which connect with the limbic system). The subthalamus lies inferior to the thalamus and dorsolateral to the hypothalamus. It contains two notable cell groups: the subthalamic nucleus (connects to the globus pallidus and sub stantia nigra and is involved with the control of movement), and the zona incerta (a rostral extension of the brainstem reticular formation). The hypothalamus has important connections with the lim bic system, a controlling influence on autonomic nervous system activity and a role in neuroendocrine function.
Basal ganglia and some connections
Caudate
Thalamus Putamen
VL
Globus pallidus
Subthalamic nucleus
Corticospinal tract
Cerebellum The cerebellum coordinates movement by maintenance of equi librium (the archicerebellum, the flocculonodular lobe and fas tigial nuclei), posture and muscle tone (the paleocerebellum, the midline vermis, paravermis and the globose and emboliform nuclei) at an unconscious level. The neocerebellum (the remain der of each cerebellar hemisphere and the dentate nucleus) is
Connections shown are with the ventral lateral (VL) nucleus of the thalamus, the neurons of which project to the cortex
Figure 4
Four basic circuits are known to occur from the cerebral cor tex, through the basal ganglia and back to the cortex, by a direct or indirect route: a motor loop is concerned with learned move ments; a cognitive loop with motor intentions; a limbic loop with emotional aspects of movement and an oculomotor loop with voluntary saccades.
Sagittal section of brainstem Tectal plate PAG Aqueduct Central grey matter
Limbic system: this system is composed of the ‘limbic lobe’ (the parahippocampal and cingulate gyri and the septal area), the hip pocampal formation (the subiculum, hippocampus and dentate gyrus), and the amygdala amongst others. Declarative memory (i.e. of new facts and events) may occur as modifications of syn apses within the hippocampus. Declarative memory requires the circuit of Papez (including the subiculum, fornix, mamil lary body, anterior thalamic nuclei and cingulate and parahippo campal gyri) to be intact in at least one hemisphere. However, the recall of memories does not seem to require intact hippocampal connections, and are probably stored as synaptic modifications in the cortex.
Tegmentum Fourth ventricle Pons
Emerging cerebrospinal fluid Pyramid Central canal Spinal cord
Diencephalon The diencephalon is continuous with the rostral midbrain and lies between it and the cerebral hemisphere, by which it is almost completely surrounded. It comprises, from superior to inferior, the epithalamus, thalamus, subthalamus and hypothalamus.
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PAG, periaqueductal grey
Figure 5
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concerned with muscular coordination, including trajectory, speed and force of movements. The cerebellar cortex consists of highly convoluted folia, which cover the white matter. Within the white matter are embedded the cerebellar nuclei, which are the source of efferent fibres to the brainstem by way of three pairs of cerebellar peduncles.
The tectum (roof) of the midbrain is formed by four col liculi – the paired superior colliculi are associated with the visual system, and the inferior colliculi with the auditory system. The intermediate region of the brainstem is known as the tegmentum, which contains the reticular formation, the ascending sensory pathways carrying general sensory information from the trunk and limbs (especially the posterior column-medial lemniscal pathways), and the descending motor corticospinal tracts – the latter two decussate in the medulla oblongata. ◆
Brainstem The third ventricle drains into an aqueduct in the midbrain, which opens into the fourth ventricle dorsal to the pons and upper medulla oblongata. From the fourth ventricle cerebro spinal fluid emerges from three apertures into the subarachnoid space. A negligible amount moves into the central canal of the spinal cord. The brainstem houses the nuclei of cranial nerves III to XII, all of which emerge anteriorly except the trochlear nerve (cranial nerve IV) (Figure 5).
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Further reading Crossman AR, Neary D. Neuroanatomy, 3rd edn. Edinburgh: Churchill Livingstone, 2005. Fitzgerald MJT, Gregory G, Mtui E. Clinical neuroanatomy and neuroscience, 5th edn. Philadelphia: Saunders, 2007.
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