Within the cerebral hemisphere lie a number of nuclear masses. The most prominent of these are the caudate nucleus, putamen and globus pallidus which lie in close proximity to the internal capsule. They are collectively referred to as the corpus striatum or basal ganglia (Figs 14.1, 14.2; see also Figs 13.3–13.9Fig. 13.3Fig. 13.4Fig. 13.5Fig. 13.6Fig. 13.7Fig. 13.8Fig. 13.9, 13.14). The amygdala, which is located within the temporal lobe, near to the temporal pole, has a similar embryological derivation but is functionally quite different. It is part of the limbic system and is considered in Chapter 16.
Figure 14.1 Horizontal section of the brain showing the relationships of the corpus striatum. Mulligan’s stain has been used to increase the contrast between cell-rich areas (blue) and white matter.
Figure 14.2 Coronal section of the brain showing the relationships of the corpus striatum. Mulligan’s stain (see legend to Fig. 14.1).
The caudate nucleus, putamen and globus pallidus are anatomically and functionally related closely to each other and are principally involved in the control of posture and movement.
Abnormalities of posture and movement resulting from their dysfunction are commonly called basal ganglia disorders. The corpus striatum has important connections with other regions of the brain, particularly the cerebral cortex, the thalamus and subthalamic nucleus of the diencephalon, and the substantia nigra of the midbrain.
For gross anatomical purposes, the putamen and globus pallidus are sometimes together called the lentiform (or lenticular) nucleus. This is because they lie close together, forming an apparently single structure. The name means ‘lentil-shaped’, but a closer analogy would be a Brazil nut or the segment of an orange. The lentiform nucleus is three-sided, having a convex lateral surface and two other surfaces that converge to a medial apex which lies against the genu of the internal capsule. The term lentiform, or lenticular, is rather archaic and of limited use, although it is still retained in certain anatomical names (such as the retrolenticular part of the internal capsule).
On phylogenetic, connectional and functional grounds, however, the putamen is more closely allied to the caudate nucleus than to the globus pallidus. The globus pallidus is, in phylogenetic terms, the oldest part of the corpus striatum and is sometimes referred to as the paleostriatum. The abbreviation pallidum is more commonly used, particularly in composite terms for afferent and efferent connections, such as subthalamopallidal or pallidothalamic.
The caudate nucleus and putamen constitute the phylogenetically more recent neostriatum and are best regarded as a single entity. The two parts are almost (but not entirely) separated by the anterior limb of the internal capsule but their gross anatomical separation is not as significant as their neuronal and functional similarities. Together, they are commonly referred to simply as the striatum.
These rather confusing relationships are summarised in Figure 14.3.
Figure 14.3 Relationships of the nuclear masses within the cerebral hemisphere.
Topographical anatomy of the corpus striatum
The striatum (neostriatum) consists of the caudate nucleus and the putamen. Their combined three-dimensional shape is reminiscent of a tadpole, when viewed laterally (Fig. 14.4).
Figure 14.4 Lateral aspect of the left caudate nucleus, putamen, amygdala and thalamus. The globus pallidus is obscured by the putamen. The course of the internal capsule is shown in red. The putamen and the head of the caudate nucleus are separated by the anterior limb of the internal capsule, except at their most rostral extent where the two are in continuity. The posterior limb of the internal capsule separates the globus pallidus and putamen from the thalamus.
The putamen lies lateral to the internal capsule and globus pallidus (Figs 14.1, 14.2; see also Figs 13.7, 13.8, 13.14Fig 13.7Fig 13.8Fig 13.14). It is separated from the globus pallidus by a thin lamina of nerve fibres, the lateral medullary lamina. Lateral to the putamen lies more white matter, sandwiched within which lies a thin sheet of grey matter, known as the claustrum. This separates the white matter into two layers, the external capsule and the extreme capsule (Fig. 14.1). Lateral to the extreme capsule lies the cortex of the insula, deep within the lateral fissure of the hemisphere.
The caudate nucleus consists of a large head and a tapering, curved tail. The head of the caudate is almost completely separated from the putamen by the internal capsule. At its rostral extremity, however, it is continuous with the putamen through and beneath the anterior limb of the internal capsule (Fig. 14.4, see also Figs 13.4–13.6Fig. 13.4Fig. 13.5Fig. 13.6). At this anterior level, the most ventral portion of the striatum is known as the nucleus accumbens, which has connections with the limbic system. The head of the caudate nucleus forms a prominent bulge in the lateral wall of the anterior horn of the lateral ventricle (Fig. 14.1, see also Figs 13.3–13.7Fig. 13.3Fig. 13.4Fig. 13.5Fig. 13.6Fig. 13.7). The tail of the caudate passes posteriorly, gradually tapering as it does so and, following the curvature of the ventricle, descends into the temporal lobe where it lies in the roof of the inferior horn (Fig. 14.4, see also Figs 13.9–13.12Fig. 13.9Fig. 13.10Fig. 13.11Fig. 13.12).
The globus pallidus lies medial to the putamen, separated from it by the lateral medullary lamina. Its medial apex nestles into the lateral concavity of the internal capsule (Fig. 14.1). The globus pallidus consists of two divisions, referred to as the external (or lateral) and the internal (or medial) segments. These are separated by a thin sheet of fibres, the medial medullary lamina (Fig. 14.1). The smaller medial segment shares many similarities, in terms of cytology and connections, with the pars reticulata of the substantia nigra in the midbrain. Although the two are separated by the internal capsule, these are best regarded as a single entity, in the functional sense.
Topographical anatomy of the corpus striatum
The corpus striatum includes the caudate nucleus, putamen and globus pallidus.
These structures are primarily concerned with the control of posture and movement.
Topographically, the putamen and globus pallidus constitute the lentiform nucleus.
The putamen and globus pallidus lie lateral to the internal capsule, deep to the cortex of the insula.
Functionally, the caudate nucleus and putamen form a single entity, the neostriatum (striatum), while the globus pallidus forms the paleostriatum.
The caudate nucleus lies in the wall of the lateral ventricle.
The largest part, or head, of the caudate lies medial to the internal capsule and forms a prominent bulge in the lateral wall of the anterior horn of the ventricle.
The curved, tapering tail of the caudate nucleus follows the curvature of the lateral ventricle into the temporal lobe.
The term substantia innominata refers to the basal part of the rostral forebrain that lies beneath the corpus striatum (see Fig. 14.7). This complex region contains several groups of neurones, one of them being the nucleus basalis(of Meynert), that project widely to the cerebral cortex and utilise acetylcholine as their neurotransmitter. These neurones undergo degeneration in Alzheimer’s disease.
Functional anatomy of the corpus striatum
Connections of the striatum
The caudate nucleus and putamen, together commonly referred to as the striatum, are best considered as a single entity since they share common neuronal organisation, neurotransmitter systems and connections (Fig. 14.5). They are often regarded as the ‘input’ portions of the corpus striatum, since the majority of afferents from other parts of the brain end here rather than in the globus pallidus.
Figure 14.5 Schematic diagram illustrating the principal connections of the corpus striatum and related nuclei. Afferents to the striatum from the intralaminar thalamic nuclei and raphe nuclei have been omitted. For the sake of clarity, all efferents from the basal ganglia system are shown to originate from the medial segment of the globus pallidus, those from the pars reticulata of the substantia nigra being omitted. Similarly, efferents from the striatum are shown to originate only from the putamen and not from the caudate nucleus.
Afferents to the striatum come from three principal sources: the cerebral cortex, the thalamus and the substantia nigra.
Corticostriatal fibres originate from widespread regions of the cerebral cortex, predominantly, but not exclusively, of the ipsilateral side. Fibres from the frontal and parietal lobes predominate. Motor regions of the frontal lobe project mainly to the putamen, where the body is represented in an inverted, approximately somatotopic fashion. More anterior regions of the frontal lobe, and other association cortices, project mainly to the caudate nucleus. For these reasons, the putamen is considered to be the most overtly motor part of the striatum, the caudate nucleus having more associative functions. Corticostriatal fibres are excitatory to striatal neurones and use glutamic acid as their transmitter.
The thalamostriatal projection comes from the intralaminar nuclei (centromedian and parafascicular nuclei) of the ipsilateral thalamus.
The nigrostriatal projection originates from the pars compacta of the ipsilateral substantia nigra of the midbrain tegmentum. The transmitter used by this pathway is the monoamine dopamine, which has both excitatory and inhibitory effects upon striatal neurones. The neurones of the pars compacta contain the dark pigment neuromelanin (Fig. 14.6), which is produced as a by-product of dopamine synthesis. The most rostral and ventral portion of the striatum, the nucleus accumbens, receives its dopaminergic input from the ventral tegmental area, which lies medial to the substantia nigra. This projection is known as the mesostriatal pathway. Other afferents to the striatum include a projection from the brain stem raphe nuclei, utilising serotonin as its transmitter.
Figure 14.6 Transverse section through the midbrain showing the substantia nigra.
Connections of the striatum
The caudate nucleus and putamen are the ‘input’ regions of the corpus striatum.
They receive afferents from the cerebral cortex, intralaminar thalamic nuclei and the pars compacta of the substantia nigra.
Efferent fibres are directed to the globus pallidus and the pars reticulata of the substantia nigra.
The efferent projections of the striatum are directed principally to the two segments of the globus pallidus and to the pars reticulata of the substantia nigra (striatopallidal and striatonigral fibres, respectively). The cells of origin are so-called medium spiny neurones, which make up the vast majority of striatal nerve cells. Generally speaking, although there is some collateralisation, separate populations of neurones project to each of the three output targets. These projections are inhibitory upon pallidal and nigral neurones and utilise GABA as their primary transmitter. In addition, a number of neuropeptides are co-localised in these efferent neurones. The cells that project to the internal segment of the globus pallidus and the substantia nigra contain both substance P and dynorphin. The projection to the external segment of the globus pallidus contains met-enkephalin.
Connections of the globus pallidus
The two segments of the globus pallidus have similar afferent connections but substantially different efferent projections. The internal segment of the globus pallidus is very similar in structure and function to the pars reticulata of the substantia nigra, from which it is separated by the internal capsule. Together, the internal pallidum and pars reticulata of the substantia nigra are regarded as the ‘output’ portion of the basal ganglia, since they are the origin of the majority of basal ganglia efferent fibres that project to other levels of the neuraxis.
Pallidal afferents arise principally from the striatum and from the subthalamic nucleus. Striatopallidal fibres are of two types, as previously noted, originating from different populations of striatal medium spiny neurones. Both utilise GABA as their primary transmitter. In addition, each contains characteristic peptide co-transmitters; fibres projecting to the external pallidal segment contain enkephalin, while those projecting to the internal pallidum contain substance P and dynorphin.
The subthalamopallidal projection originates in the subthalamic nucleus of the caudal diencephalon (Figs 14.7, 14.8). This small structure is located beneath the thalamus, lying against the medial border of the internal capsule. In coronal sections, it has the appearance of a biconvex lens. Subthalamopallidal fibres pass laterally through the internal capsule, contributing to a fibre system known as the subthalamic fasciculus (Fig. 14.8), and terminate in both segments of the globus pallidus, although termination is more dense in the internal segment.
Figure 14.7 Coronal sections through the corpus striatum and diencephalon. Loyez method for myelin.
(Sections courtesy of the National Museum of Health and Medicine, Armed Forces Institute of Pathology, Washington, DC, USA).
Figure 14.8 Coronal section through the corpus striatum and diencephalon illustrating the efferent projections of the globus pallidus.
The subthalamopallidal pathway is excitatory to pallidal neurones, using glutamic acid as its transmitter. The subthalamic nucleus also sends similar fibres to the pars reticulata of the substantia nigra, the other ‘output’ part of the basal ganglia system. The subthalamopallidal and subthalamonigral pathways have a pivotal role in the normal function of the basal ganglia and in the pathophysiology of basal ganglia disorders.
The two pallidal segments have different efferent projections. The external segment projects principally to the subthalamic nucleus. Pallidosubthalamic fibres pass medially through the internal capsule in the subthalamic fasciculus. This projection is inhibitory and uses GABA as its transmitter. The internal segment of the globus pallidus, together with the pars reticulata of the substantia nigra, projects primarily to the thalamus (ventral lateral, ventral anterior and centromedian nuclei), with a smaller projection to the brain stem tegmentum. These output neurones are all inhibitory and utilise GABA as their transmitter.
Pallidothalamic fibres take one of two routes to reach their target (Fig. 14.8). Some fibres pass round the anterior margin of the internal capsule as the ansa lenticularis, while others pass through the internal capsule as the lenticular fasciculus. The fibres continue to course medially and then loop dorsally and laterally as the thalamic fasciculus to enter the thalamus from its ventral aspect. In following this trajectory, pallidothalamic fibres circumnavigate a cellular region of the subthalamus known as the zona incerta, which lies between the thalamus and the subthalamic nucleus.
Pallidothalamic fibres constitute the main outflow from the basal ganglia. Their thalamic target nuclei (ventral anterior and ventral lateral), in turn, project excitatory, glutamatergic, fibres to the motor regions of the frontal lobe, principally the primary motor and supplementary motor cortices. A smaller contingent of medial pallidal efferent fibres passes caudally to terminate in the brain stem tegmentum in the nucleus tegmenti pedunculopontinus(pedunculopontine nucleus), which lies at the boundary between midbrain and pons, surrounding the superior cerebellar peduncle (Fig. 14.5, see also Fig. 13.12). This region has been termed the mesencephalic locomotor regionin lower mammals, since it is involved in the regulation of quadrupedal progression.
The pars reticulata of the substantia nigra is regarded as a homologue of the internal segment of the globus pallidus and, thus, has a similar status as the origin of basal ganglia output neurones. Like the internal pallidum, the pars reticulata receives fibres from the striatum and the subthalamic nucleus. The projection from the striatum is somatotopically organised, both in the pallidum and nigra, such that pallidal neurones are associated primarily with limb movements, whereas nigral cells control the axial musculature, including the extraocular muscles. As already noted, efferents from the internal pallidum project to the ventral anterior, ventral lateral and centromedian thalamic nuclei and to the pedunculopontine nucleus. Efferents of the pars reticulata of the substantia nigra also pass to a subregion of the ventral lateral thalamus, to the superior colliculus and to the brain stem reticular formation (including the pedunculopontine nucleus).
Connections of the globus pallidus
The globus pallidus consists of two segments: external and internal.
Both pallidal segments receive afferent fibres from the striatum and the subthalamic nucleus.
The external pallidal segment projects to the subthalamic nucleus.
The internal pallidal segment is homologous to the pars reticulata of the substantia nigra; the two structures are the ‘output’ regions of the basal ganglia.
The internal pallidal segment projects to the thalamus (ventral anterior, ventral lateral and centromedian nuclei) and brain stem (pedunculopontine nucleus).
Normal functions of the basal ganglia
The basal ganglia are sometimes referred to as components of the so-called ‘extrapyramidal motor system’. This term was coined to distinguish the symptoms seen clinically in diseases of the basal ganglia and related structures such as the substantia nigra and subthalamic nucleus, from the symptoms observed following stroke in the internal capsule, the latter being thought to be caused by destruction of the pyramidal tract. As understanding of the functional anatomy of the motor system has increased, it has become apparent both that the pyramidal and extrapyramidal systems are intimately related rather than separate, and also that so-called pyramidal signs are not all attributable to dysfunction of the pyramidal tract itself. The term extrapyramidal is, therefore, somewhat outdated but is still in widespread use.
Current concepts of the role of the basal ganglia consider that their function is to facilitate behaviour and movements that are required and appropriate in any particular context and to inhibit unwanted or inappropriate movements. How this might be achieved can be explained with reference to the internal connections of the basal ganglia (Fig. 14.5).
When a movement is initiated from the cerebral cortex, impulses discharge not only through corticospinal and corticobulbar pathways but also through the corticostriatal projection to the neostriatum. These glutamatergic fibres cause excitation of striatal medium spiny neurones. The striatum has two routes by which it is able to control the activity of basal ganglia output neurones in the internal segment of the globus pallidus and the pars reticulata of the substantia nigra. The first of these is the so-called ‘direct pathway’, consisting of striatopallidal and striatonigral neurones which directly inhibit internal pallidal or pars reticulata neurones. This mechanism has been shown to operate in experimental electrophysiological studies in primates, where basal ganglia output neurones associated with a particular body part or muscle group show a pause in their action potential discharge during movement of that region. This has been shown in the internal pallidum for limb movements and in the substantia nigra, pars reticulata for eye movements. Since internal pallidal and pars reticulata output neurones are themselves inhibitory, this leads to disinhibition of target neurones, including those of the motor thalamus. The resulting increase in the activity of thalamic neurones causes excitation of the cells of the cerebral cortex. The effect of activation of the direct pathway is, therefore, to support or facilitate ongoing movements, through this positive feedback to the cortex.
The second route by which striatal neurones can influence the output of the basal ganglia is the so-called ‘indirect pathway’, via the subthalamic nucleus. Efferents from the striatum terminate in the external pallidal segment and their activation induces inhibition of external pallidal neurones. The principal efferent projection of the external pallidum is to the subthalamic nucleus which, therefore, becomes disinhibited. The resultant increase in discharge of subthalamic neurones causes activation of internal pallidal and nigral neurones and, in turn, inhibition of thalamic and cortical cells. This has the effect of inhibiting unwanted movements.
Pathophysiology of basal ganglia disorders
Studies on the post-mortem brains of patients with Parkinson’s disease and experimental animal studies have provided insight into the pathophysiological mechanisms that underlie the appearance of parkinsonian symptoms (Fig. 14.9). Normally, dopamine appears to exert an excitatory influence upon striatal neurones of the ‘direct’ projection to the internal pallidal segment, and an inhibitory effect upon neurones of the ‘indirect’ pathway that projects to the external pallidal segment. Loss of striatal dopamine, therefore, causes abnormal underactivity of the direct pathway and disinhibition of internal pallidal neurones. Simultaneously, overactivity of the indirect projection leads to inhibition of external pallidal neurones, disinhibition of the subthalamic nucleus, and thus excessive excitatory drive of internal pallidal cells. Changes in both the direct and indirect pathways, thus, compound to exacerbate the abnormal overactivity of internal pallidal output cells, inducing akinesia.
Figure 14.9 Schematic diagram illustrating how activities in basal ganglia and related nuclei become disordered in Parkinson’s disease and chorea. Overactive pathways are shown by solid lines; underactive pathways are shown by interrupted lines. For identification of structures, see Fig. 14.5.
The archetypal basal ganglia disease in which excessive, unwanted, abnormal movements (dyskinesias) occur is Huntington’s disease (Huntington’s chorea). Within the striatum, there is particular attrition of the cells that project to the external segment of the globus pallidus (the ‘indirect’ projection), at least early on in the condition. This leads to disinhibition of external pallidal neurones and inhibition of the subthalamic nucleus. Internal pallidal neurones, therefore, become abnormally underactive and unwanted, involuntary movements ensue. Similar abnormal movements (chorea) occur as a complication of the long-term treatment of Parkinson’s disease with l-DOPA. The underlying neural mechanism is similar but, in this case, there is both relative underactivity of the indirect pathway and overactivity of the direct pathway (Fig. 14.9).
Involuntary movement disorders
Unilateral basal ganglia lesions produce their effects on the contralateral side of the body, as is the case with cerebral hemisphere lesions, but distinct from cerebellar disorders. Basal ganglia dysfunction does not cause paralysis, sensory loss or ataxia, but leads to abnormal motor control, alterations in muscular tone and the emergence of abnormal, involuntary movements, or dyskinesias.
Abnormal motor control may consist of slowness of movement (bradykinesia) or poverty of movement (hypokinesia, akinesia). The initiation, sequencing and cessation of movement are disrupted. Normal posture cannot be maintained and ‘associated’ limb movements are lost, e.g. arm swinging when walking.
Tone may be increased throughout the range of passive movement (rigidity) and the hypertonia may be continuous (plastic) or discontinuous (‘cogwheel’). Alternatively, hypotonia may occur.
Dyskinesias may be manifest in various ways and describe the abnormal movements, not the underlying disease. Chorea is a sequence of rapid, asymmetrical, and fragmented (quasi-purposeful) movements usually affecting the distal limb musculature. Athetosis consists of slow, sinuous, writhing movements. Sometimes movements share more than one characteristic; hence the term choreo-athetosis. Dystoniarefers to sustained muscular contractions that give rise to abnormal postures or contortions. Tremor is a to-and-fro, sinusoidal movement that may be maximal at rest (resting tremor) or on action (action or postural tremor).
Tics are stereotyped movements, often highly characteristic of the individual, sometimes multiple and frequently influenced by emotional stress.
Myoclonus describes sudden, shock-like movements which are usually bilateral and especially affect the upper limbs.
Basal ganglia diseases
Parkinson’s disease is a chronic neurodegenerative disease, usually occurring in the elderly. It is usually of unknown cause (idiopathic) although there are genetically determined forms which may be inherited. It is characterised by akinesia, a flexed posture, rigidity and a resting tremor. The pathological hallmark of Parkinson’s disease is degeneration of the dopaminergic neurones of the pars compacta of the substantia nigra (Fig. 14.10), and depletion of striatal dopamine levels (Fig. 14.11). The most effective medical treatment currently available for the condition is administration of levodopa (l-DOPA), the immediate metabolic precursor of dopamine; dopamine receptor agonists may also be used. Levodopa is converted to dopamine and restores normal striatal function, a strategy that can often be used to minimise symptoms for many years. When drug therapy fails, neurosurgical ablation or electrical stimulation of the subthalamic nucleus or the internal segment of the globus pallidus can help the patient.
Figure 14.10 Approximately transverse sections through the lateral half of the midbrain, showing degeneration and depigmentation of the substantia nigra, pars compacta in Parkinson’s disease.
(Courtesy of Professor D Mann, Clinical Neurosciences, Hope Hospital, University of Manchester, Manchester, UK.)
Figure 14.11 Positron emission tomography (PET) scans, representing horizontal sections through the brain at the level of the striatum. Anterior is towards the top in each case. The top scans are from a normal individual and the bottom ones from a patient with Parkinson’s disease. The scans on the left were made using the tracer [18F]-dopa. This is taken up by intact dopaminergic nerve terminals and, therefore, acts as an index of the integrity of the nigrostriatal pathway. There is reduced labelling in the striatum of the parkinsonian patient. The scans on the right were made using the tracer [11C]-raclopride. This binds to dopamine receptors located on striatal neurones that receive input from the nigrostriatal pathway. These receptors remain intact in the parkinsonian patient.
(Courtesy of Professor D J Brooks, Hartnett Professor of Neurology, Imperial College, London, UK.)
Huntington’s disease is a chronic degenerative disease inherited in an autosomal dominant manner and characterised by chorea and progressive dementia. Pathologically, there is progressive degeneration of the striatum and cerebral cortex. Hepatolenticular degeneration (Wilson’s disease) is an inherited disorder (autosomal recessive) of copper metabolism. Basal ganglia changes lead to choreo-athetosis and progressive dementia in childhood and youth. Sydenham’s chorea is now rare but was formerly a common manifestation of rheumatic fever in young females, causing abnormal behaviour and generalised chorea (St Vitus’ dance).
Levodopa-induced dyskinesia is a complication of the long-term treatment of Parkinson’s disease with levodopa, and tardive dyskinesia is a long-term complication of the treatment of schizophrenia with neuroleptic drugs. Hemiballism is a rare condition characterised by violent choreiform movements of the limbs on one side of the body. It is caused by a lesion, usually of cerebrovascular origin, of the contralateral subthalamic nucleus. Dystonia may arise as an inherited disorder in children and is usually generalised. In adults, focal or segmental dystonias affect the arm and hand (writer’s cramp), leg, neck (torticollis) or face and mouth (orofacial dyskinesia).
Basal ganglia function
The basal ganglia historically were referred to as parts of the extrapyramidal motor system to distinguish basal ganglia disorders from those of the pyramidal tract. However, both systems are intimately related.
The basal ganglia facilitate purposeful behaviour and movement via the ‘direct pathway’ and inhibit unwanted movements via the ‘indirect pathway’.
Lesions of the basal ganglia produce effects on the contralateral side of the body.
Diseases of the basal ganglia are typified by Parkinson’s disease, in which there is poverty of movement, and Huntington’s disease, which is associated with dyskinesias.