SPSC2005 / HCSCGS17 CENTRAL NERVOUS SYSTEM : ORGANISATION, FUNCTION AND BLOOD SUPPLY Material relating to this lecture can

be found in Atkinson & McHanwell Chapters 6, 8, 9, and 10 (consult index for individual topics) and Chapter 13 of Seeley et al. The central nervous system (CNS) consists of the brain and spinal cord. The CNS is the control centre of the nervous system and is responsible for consciousness. It receives sensory information from the periphery, integrates incoming information and generates co-ordinated motor activity. Both brain and spinal cord are enclosed in bone (skull and vertebral column). OVERALL ORGANISATION OF THE BRAIN The organisation of the brain can best be explained by looking at a mid-sagittal section. The brain comprises a central core (continuous with the spinal cord) which is enveloped on either side by the deeply folded cerebral hemispheres. The brain has 3 major subdivisions - FOREBRAIN, MIDBRAIN and HINDBRAIN - each of which is further subdivided into functionally distinct regions During embryonic development the CNS starts as a hollow tube and the cerebral hemispheres grow out from either side of the forebrain to increase the area of the cerebral cortex; as the hemispheres grow they expand backwards over the core of the brain, covering much of the central structures. REGIONS OF THE BRAIN FOREBRAIN: CEREBRAL HEMISPHERES - concerned with higher perceptual, cognitive and motor functions Cerebral cortex on surface Basal ganglia underlying (see below) DIENCEPHALON Thalamus is a key relay station - relays information (especially sensory) from other CNS regions (especially spinal cord) to the cerebral cortex Hypothalamus controls autonomic and endocrine integration; controls hormone release Pituitary gland - hormone secretion Forebrain gives rise to cranial nerves I and II MIDBRAIN: Superior colliculus controls eye movements Inferior colliculus processes auditory information Midbrain gives rise to cranial nerves III (Oculomtor) and IV (Trochlear) Cerebellum coordinates motor activity, posture, equilibrium; integrates information from various sources and coordinates activities such as contraction and relaxation of opposing muscles during walking, or visual and motor skills; important for pattern generation, timing movement sequences, modifying reflexes; involved in motor learning. Many cerebellar functions are "automatic", e.g. writing a signature, speaking familiar words Pons contains neurons that relay information between the cerebral hemispheres and the cerebellum; gives rise to cranial nerve V (trigeminal) Medulla gives rise to cranial nerves VI, VII, VIII, IX, X, XII The midbrain, pons and medulla collectively form the BRAINSTEM During development the forebrain comes to lie at right angles to the longitudinal axis of the brain stem and spinal cord, the cerebral hemispheres develop as outgrowths of the forebrain serving to increase the area of the cerebral cortex; as each hemisphere grows it expands backwards covering much of the brainstem structure. CEREBRAL HEMISPHERES The outer layer of the cerebral hemispheres comprises a layer of grey matter - the CEREBRAL CORTEX; it is responsible for higher order cognitive functions. The two hemispheres are involved in processing specific information They are connected by a thick bundle of nerve fibres the CORPUS CALLOSUM The cerebral cortex is extensively folded with a system of highly organised grooves and ridges A groove is called a SULCUS (plural SULCI) Deepest grooves are called FISSURES A ridges is called a GYRUS (plural GYRI) The two hemispheres are separated by the LONGITUDINAL FISSURE Each hemisphere is divided into 5 LOBES Four of these are readily visible on the surface and are named for the bones of the skull that overlie them FRONTAL, TEMPORAL, PARIETAL, OCCIPITAL Frontal lobe most anterior; separated from parietal by CENTRAL SULCUS Temporal lobe inferior to frontal lobe and separated from it by the LATERAL FISSURE Occipital and parietal lobes separated by the PARIETO-OCCIPITAL SULCUS The fifth lobe is "buried" beneath the frontal and temporal lobes; it is called the INSULA or CENTRAL LOBE. On either side of the central sulcus is a prominent gyrus PRECENTRAL GYRUS and POSTCENTRAL GYRUS Cortex of precentral gyrus (in frontal lobe) is the PRIMARY MOTOR CORTEX the neurons in this region generate motor output and transmit it to the motor neurons in spinal cord and brain stem that innervate skeletal muscles. The frontal lobe also contains the motor speech area Brocas area. Cortex of postcentral gyrus (in parietal lobe) is the PRIMARY SOMATOSENSORY CORTEX this area of cortex processes all the incoming information concerned with somatic sensation.

HINDBRAIN:

Temporal lobe contains auditory cortex, and also contains the area of the brain responsible for speech and language comprehension (Wernickes area) which also extends into the parietal lobe. Occipital lobe contains visual cortex Insula largely concerned with visceral and autonomic function (e.g.taste)

SOMATOTOPIC ORGANISATION Specific regions of the body are represented by specific areas of both the primary motor cortex and the primary somatosensory cortex this is called SOMATOTOPIC REPRESENTATION of body parts. The size of the area that represents a given body region depends on the degree of sensitivity and fine motor control required within that region, so areas like fingers and lips have a large representation on the cortex. The relative representation of body parts can be represented pictorially by the MOTOR HOMUNCULUS and the SENSORY HOMUNCULUS. BASAL GANGLIA Lying deep below the cortex and the underlying white matter are several large collections of neurons known as the BASAL GANGLIA They receive input from the cerebral cortex and feed back to the cortex via the thalamus; these feedback loops are important in regulating motor functions and muscle tone. If these structures are damaged or abnormal it doesnt result in paralysis, but produces involuntary movements. Both Parkinsons disease and Humtingtons chorea are disorders of the basal ganglia Three important components of the basal ganglia are: CAUDATE NUCLEUS PUTAMEN GLOBUS PALLIDUS Caudate nucleus and putamen are collectively called the STRIATUM Another deep structure that is functionally related to the basal ganglia is the SUBSTANTIA NIGRA (midbrain structure). Its name comes from the fact that some of its cells contain the dark pigment melanin which makes the structures appear black. These cells secrete the inhibitory neurotransmitter dopamine. Feedback information is also passed between the basal ganglia and the substantia nigra; this feedback is inhibitory. In Parkinsons disease dopamine-releasing cells degenerate, removing the inhibitory feedback and leads to uncontrolled muscle tremor, and slow, impaired movement. ORGANISATION OF THE SPINAL CORD Divided into cervical, thoracic, lumbar, sacral and coccygeal regions Gives rise to 31 pairs of segmental spinal nerves (C 8, T 12, L 5, S 5, C 1) Sensory information carried by afferent nerve fibres enters via dorsal roots Motor commands carried by efferent nerve fibres leave via ventral roots Cell bodies of neurons are located in central area of grey matter Ventral horn of grey matter contains cell bodies of motor neurons Dorsal horn of grey matter contains cell bodies of sensory interneurons Primary afferent fibres from muscle spindles synapse directly with motor neurons in the ventral horn All others synapse with sensory interneurons in the dorsal horn Peripheral white matter contains bundles of nerve axons (FIBRE TRACTS) running to and from the brain So in the spinal cord grey matter is in the centre and white matter round the outside edge nearer the surface. The organisation of grey and white matter is similar in the brainstem, but remember that in the cerebral hemispheres the grey matter is nearer the surface peripheral and the white matter lies internally. FIBRE TRACTS IN WHITE MATTER OF THE BRAIN Fibres in the white matter are axons arising from nerve cell bodies projecting to other nerve cells (forming synapses with cell bodies, or dendritic processes, or even other axons) The sending and receiving nerve cell bodies may be inside or outside the brain, depending on the pathway There are three main categories of fibres: ASSOCIATION FIBRES - wholly confined to one hemisphere; short fibres that interconnect cortical areas of adjacent gyri, or long fibres that interconnect remote cortical areas in different lobes COMMISSURAL FIBRES - connect cortical cells on one hemisphere to cells in the corresponding area of the other hemisphere. PROJECTION FIBRES - connect the cortex to subcortical structures and nuclei (subcortical means "beneath the cortex"). There are two main types Descending or efferent fibres - originate in the cortex (from cell bodies in the grey matter) and project down to the basal ganglia, thalamus, hypothalamus, brain stem, and spinal cord Ascending or afferent fibres project to the cortex, mostly from the thalamus which receives inputs from secondary (second order) afferent fibres from many other regions TRACTS BETWEEN BRAIN AND SPINAL CORD Neural pathways between brain and periphery are arranged in tracts. Both motor and sensory tracts cross over from one side of the CNS to the other so that muscles and other target organs on the right side of the body are associated with and controlled by the left hemisphere, and vice versa. Sensory pathways cross (decussate) at the level they enter the spinal cord or in the medulla, motor pathways mostly cross within the medulla. MOTOR PATHWAYS Motor pathways run from the primary motor cortex to the periphery and are TWO-NEURON PATHWAYS involving an UPPER MOTOR NEURON in the cortex the axon of which descends to either the brain stem or the spinal cord where it synapses with a LOWER MOTOR NEURON that will send its axon (via a spinal or cranial nerve) to the muscle or other target in the periphery. These motor pathways are generally referred to as the PYRAMIDAL TRACTS there are two types of pyramidal tract The CORTICOSPINAL tract provides a direct route for motor neurons from the cortex to the spinal cord where they synapse with spinal motor neurons that supply prime locomotor muscles; so the upper motor

neurons synapse in the ventral horn of the spinal cord and the fibres of the lower motor neurons run out to the periphery via spinal nerves. Fibres of the corticospinal tract cross over in the medulla. The CORTICOBULBAR tract provides a route from cortex to the brainstem where they synapse with cranial motor neurons of the oculomotor, trigeminal, facial, vagal and hypoglossal nerves that supply the muscles of the head and neck; the upper motor neurons synapse in the brainstem and the fibres of the lower motor neurons run out to the periphery via cranial nerves. Fibres of the corticobulbar tract cross over in within the brainstem (largely pons and medulla). **This tract is therefore important in motor functions of speech production** In all motor pathways, the fibres of upper motor neurons pass down from the cerebral cortex through a region of the forebrain called the INTERNAL CAPSULE. SENSORY PATHWAYS Sensory (afferent) pathways project to the primary sensory cortex via the THALAMUS they are THREE-NEURON PATHWAYS The DORSAL COLUMN - MEDIAL LEMNISCAL pathway conveys information about discriminated touch, vibratory sense and proprioception. Primary sensory axons enter the spinal cord and divide into branches. One branch enters the dorsal horn and terminates in the deep dorsal horn or the ventral horn; another branch turns inferiorly to terminate in a similar way, in the dorsal horn of lower segments. The ascending branch enters the dorsal columns and ascends to the medulla to synapse in the dorsal column nuclei. Second-order neurons then cross to the other side of the medulla and ascend to the region of the brain called the thalamus, where they synapse with third-order neurons that convey the information to a region of the cerebral cortex called the somatosensory cortex. The SPINOTHALAMIC tract conveys information from trunk and limbs. Primary sensory axons terminate in the dorsal horn of the spinal cord where they synapse with second-order neurons. Second-order neurons cross to the other side of the spinal cord immediately and ascend to the thalamus where they synapse with third-order neurons that project to the somatosensory cortex. The TRIGREMINAL SENSORY pathway conveys information from the head and neck, especially from cranial nerves V, VII, IX and X. Primary sensory axons terminate in the trigeminal nucleus of the pons, cross over to the other side of the pons, and then ascend in the trigeminothalamic tract through the midbrain to the thalamus. Third-order neurons in the thalamus then ascend into somatosensory cortex.

VENTRICLES, MENINGES AND CEREBROSPINAL FLUID (CSF) The whole of the CNS is covered by a set of membranes called the MENINGES and has at its core a system of fluid-filled cavities called VENTRICLES in the brain and SPINAL CANAL in the spinal cord. The surfaces and central cavities of the CNS are bathed by a clear, colourless fluid called CEREBROSPINAL FLUID (CSF). VENTRICLES A series of interconnected fluid-filled spaces in the core of the forebrain and brainstem. Adult derivative of the fluid-filled space in the centre of the embryonic neural tube. 1ST and 2ND VENTRICLES, also called the LATERAL VENTRICLES, lie in the centre of cerebral hemispheres (forebrain) 3RD VENTRICLE lies in structures of the diencephalon (forebrain). 4TH VENTRICLE lies in structures of the hindbrain. CEREBRAL AQUEDUCT lies at the centre of the midbrain and joins the 3rd and 4th ventricles. THE MENINGES Three layers of membranes covering the entire central nervous system DURA MATER - outer layer of the meninges - tough and thick has connections to surrounding bone and restricts movement of the brain within the skull so protects brain from movements that may stretch and break brain blood vessels. Beneath the dura lies the subdural space, which contains a small amount of tissue fluid. In the cranium the dura consists of two layers, between which lie the cerebral venous sinuses ARACHNOID MATER middle layer beneath which is the subarachnoid space, which contains the cerebrospinal fluid (CSF) PIA MATER - innermost membrane - relatively delicate - adheres closely to the surface of the brain, following its contours. Pia is connected to arachnoid by fine strands of connective tissue called arachnoid trabeculae The subarachnoid space does not communicate with the subdural space, but is continuous with the ventricular system of the brain through three small openings (called foramina) in the roof of the fourth ventricle: foramen of Magendie (on the midline) foramina of Luschka (one on each side) CEREBROSPINAL FLUID (CSF) Mostly formed by the cells in the CHOROID PLEXUSES - rich networks of blood vessels lining the floor of the lateral ventricles and roofs of the third and fourth ventricles Also produced by ependymal cells, the epithelial cells that line the whole ventricular system Composition similar to blood, but without any cells or proteins Circulates through the ventricles and spinal canal, and around the outside of the brain and spinal cord Diffuses across arachnoid granulations to join venous blood in one of the dural sinuses (superior longitudinal sinus) see below under Venous drainage Volume of CSF 100-150 ml and it has a rapid turnover of around 3-4 exchanges per day.

CEREBRAL BLOOD SUPPLY The arterial blood supply to the brain is supplied by two pairs of arteries VERTEBRAL and INTERNAL CAROTID arteries The VERTEBRAL ARTERIES arise from the subclavian artery and ascend through the neck through holes in the cervical vertebrae and join together at the base of the pons to form the BASILAR ARTERY At the top of the pons the basilar artery divides to become the POSTERIOR CEREBRAL ARTERIES (left and right) which form part of the CIRCLE OF WILLIS The INTERNAL CAROTIDS arise at the bifurcation of the common carotids, and ascend in the neck without further branching At the base of the brain they divide three ways (the same on the left and right sides): o one branch projects upwards as the MIDDLE CEREBRAL ARTERY o one branch projects backwards as the POSTERIOR COMMUNICATING ARTERY, which joins to the posterior cerebral artery o one branch projects forwards as the ANTERIOR CEREBRAL ARTERY The two anterior cerebral arteries come very close together; they are joined by a very short artery, the ANTERIOR COMMUNICATING ARTERY, which completes the CIRCLE OF WILLIS The CIRCLE OF WILLIS equalises pressure within the arterial supply to the brain and also provides a safety mechanism - if one of the supplying arteries gets blocked, the "circle" will still provide the brain with blood. Many other vessels branch off from the basilar artery and the circle of Willis, ramifying over the surface of the brain and supplying the choroid plexuses Blood vessels (arteries, arterioles, veins, venules) travel between the arachnoid and pia mater The very small vessels that nourish the brain are carried by the pia as it follows the contours It is important to know the territory of the cerebral arteries to understand which functions will be impaired if a blockage occurs in one of them. ANTERIOR CEREBRAL ARTERY supplies the medial surface of the frontal and parietal lobes and also a strip about 1cm wide on the lateral surface of these lobes. This territory includes the lower limb region of the primary motor cortex and primary somatosensory cortex. POSTERIOR CEREBRAL ARTERY supplies the medial and inferior surfaces of the temporal and occipital lobes (In fact supplies most of the occipital lobe). This territory includes the visual cortex. MIDDLE CEREBRAL ARTERY supplies the lateral surfaces of frontal, temporal and parietal lobes and also the insula. This territory includes most of the primary motor and somatosensory cortex (including the regions that represents the upper part of the body), auditory cortex, areas for production and comprehension of speech and language (Brocas and Wernickes areas), and much of the association cortex. Venous drainage Venous blood drains via the cerebral veins from the brain into epithelium-lined cavities in the dura called venous dural sinuses and from there into the internal jugular veins. VASCULAR TRAUMA STROKES occur when the vascular supply to the brain is either interrupted (infarct) or ruptured (haemorrhage). Strokes are therefore also called CEREBROVASCULAR ACCIDENTS or CVAs. An infarct occurs when the blood supply to the brain is stopped preventing parts of the brain becoming perfused and oxygenated. This can happen as a result of either a blood clot (thrombosis) or from occlusion of a blood vessel by some other means. If blood flow remains interrupted, neurons will start to die from lack of oxygen. Paralysis or aphasia (loss of speech) are possible consequences of a stroke. Aneurysms are swellings or thinning of artery walls which can spontaneously haemorrhage (bleed); they often occur at a weak point of a pulsating artery where it branches, typically at the Circle of Willis.