UNIVERSITY OF JORDAN FACULTY OF MEDICINE DEPARTMENT OF PHYSIOLOGY & BIOCHEMISTRY NEUROPHYSIOLOGY (MEDICAL), SPRING 2014 Textbook of Medical Physiology by: Guyton & Hall, 12 th edition 2011 Eman Al-Khateeb, Professor of Neurophysiology No. 3 BASIC SOMATOSENSORY PATHWAY The somatosensory system includes multiple types of sensation from the body - light touch, pain, pressure, temperature, and joint and muscle position sense (also called proprioception). However, these modalities are lumped into three different pathways in the spinal cord and have different targets in the brain. The first modality is called discriminative touch, which includes touch, pressure, vibration perception and conscious proprioception. The second grouping is pain and temperature, which is just what it sounds like, and also includes the sensations of itch and tickle and sexual sensation. The third modality is called subconscious proprioception, and includes receptors for what happens below the body surface: muscle stretch, joint position, tendon tension, etc. This modality primarily targets the cerebellum, which needs minute-by-minute feedback on what the muscles are doing. These modalities differ in their receptors, pathways, and targets, and also in the level of crossing. Any sensory system going to the cerebral cortex will have to cross over at some point, because the cerebral cortex operates on a contralateral (opposite side) basis. The discriminative touch system crosses high - in the medulla. The pain system crosses low - in the spinal cord. The proprioceptive system is going to the cerebellum, which (surprise!) works ipsilaterally (same side). Therefore this system doesn't cross. Discriminative touch: Sensation enters the periphery via sensory axons. All sensory neurons have their cell bodies sitting outside the spinal cord in a clump called a dorsal root ganglion. The sensory neurons are unique because unlike most neurons, the signal does not pass through the cell body. Instead the cell body sits off to one side, without dendrites, and the signal passes directly from the distal axon process to the proximal process. The sensory axons (primary afferents) ascend in the dorsal white matter of the spinal cord (dorsal columns or the posterior columns). The posterior columns can actually be divided into two separate tracts. The midline tracts are tall and thin, and were given the name gracile fasciculus (gracile means slender, and fasciculus means a collection of axons). The outer tracts are more wedge shaped, and were given the name cuneate fasciculus (cuneate means wedge-shaped). The gracile fasciculus is carrying all of the information from the lower half of the body (legs and trunk), while the cuneate fasciculus is carrying information from the upper half (arms and trunk) At the medulla, the primary afferents finally synapse. The gracile fasciculus axons synapse in the gracile nucleus, and the cuneate axons synapse in the cuneate nucleus. The neurons receiving the synapse are now called the secondary afferents. The secondary afferents leave these nuclei and immediately cross, lining up in the ventral 1
medulla. The new tract that they form is called the medial lemniscus ("midline ribbon"), and it will ascend all the way through the brainstem to the thalamus, (thalamus is the clearinghouse for everything that wants to get into cortex). Once in thalamus, the secondary afferents synapse in a thalamic nucleus called the ventrolateral posterior nucleus (VPL). The thalamocortical afferents (from thalamus to cortex) travel up through the internal capsule to get to primary somatosensory cortex, the end of the pathway. Primary somatosensory cortex is located in the postcentral gyrus, which is the fold of cortex just posterior to the central sulcus. Here is a schematic of the posterior columns pathway, to remind you: Now, think briefly about some possible lesions. If you cut this pathway, most of the discriminative touch sensation will be lost (not all, because some sneaks into other pathways for redundancy). Where would the sensory loss be if you cut? 1) The left gracile fasciculus? 2) The left dorsal columns (gracile & cuneate)? 3) The right medial lemniscus, in the medulla? 2
4) The left internal capsule? Answer these for yourself, with the diagram if necessary, and then see the answers down. + + + 1) The left leg and lower left trunk. 2) The left side of the body below the level of the cut. 3) The entire left body, from the neck down. 4) The entire right body (including the face, because the face joins the pathway in the pons, but we will get to that later). 3
Clinical correlate; Lesions of the dorsal column result in loss of joint position sensation, vibratory and pressure sensations, and two point discrimination. There is loss of the ability to identify the characteristics of an object, called Astereognosis (e.g. size, consistency, form, shape), using only the sense of touch. Typically, dorsal column-medial lemniscal lesions are evaluated by testing vibratory sense using a 128 Hz tuning fork. Romberg sign is also used to distinguish between lesions of the dorsal column and the midline (Vermal area) of the cerebellum. Romberg sign is tested by asking the patients to place their feet together. If there is a marked deterioration of posture (if the patient sways) with the eyes closed, this is a positive Romberg sign suggesting that the lesion in the dorsal columns (or dorsal roots of spinal nerves). With the eyes open, interruption of proprioception input carried by the dorsal columns can be compensated for by visual input to the cerebellum. Therefore, if the patient has balance problems and tends to sway with their eyes open, this is indicative of cerebellar damage. Spatial Orientation: Fibers from the lower part of the body lie medially; fibers from higher segments form successive layers laterally. In Thalamus the spatial orientation is maintained. The most lateral portions of the ventrobasal complex represent the lower part of the body, while the medial part of the complex represent fibers from head and neck. The left side of the body is represented in the right side of the Thalamus & vice versa (Because of crossing of medial lemniscus at the medulla). Organization of somatosensory cortex: In general about 90 % of the cortex is composed of six layers of neurons; the olfactory cortex and hippocampal formation are three-layered structures. In the somatosensory cortex, layer 1 is next to surface, the neurons in each layer perform functions different from those in the other layers. Layer 4 is the station for the incoming sensory signals & from it they spread toward the surface & toward the deeper layers. Layers 1, 2, &3 are for inter-cortical connections. Layer 5 send fibers to basal ganglia, brainstem & SC. Layer 6 send fibers to Thalamus. *The neurons of the somatosensory cortex are arranged in vertical columns extending all the way through the six layers of the cortex. Each column has a diameter of 0.3-0.5 mm & contain 10000 neurons. Each column serves single specific sensory modality. *In the most anterior portion of the postcentral gyrus (Broadmann's area 3a) vertical columns respond to muscle, tendon, or joint stretch receptors, many of these signals spreads to the nearby motor cortex (pre-central gyrus). Posterior vertical columns respond to slowly adapting cutaneous receptors &still further posteriorly columns are sensitive to deep pressure. In the most posterior part it gets even more complicated where 6 % of vertical columns respond only when a stimulus moves across the skin in a particular direction (High order of interpretation). The process becomes even more complex as the signals spread further to the posterior & central parietal lobe (somatic association area). 4
Somatic Sensory Cortex: (Post central gyrus). It is situated posterior to the central fissure & it involves the anterior half of the parietal lobe while the posterior half is involved with still higher levels of interpretation to sensory signals. Primary somatosensory cortex; The postcentral gyurs corresponds to Brodmann areas 3, 1, and 2 and contains primary somatosensory cortex. This area has high degree of localization; it receives sensory information exclusively from the opposite side of the body. There is a somatotropic representation of the body with head, neck, upper limb, and trunk represented on the lateral aspect of the hemisphere, and pelvis and lower limb represented medially. Some area in the body are represented by large areas in the primary somatosensory cortex e.g. Lips (the greatest area of all), followed by the Thumb & the Face, whereas the trunk & lower part of the body are represented by relatively small areas. These areas are concerned with discriminative touch, vibration, position sense, pain, and temperature. Lesions in somatosensory cortex result in impairment of all somatic sensations on the opposite side of the body, including face and scalp. 5
The Sensory Homunculus in postcentral gyrus (Area 3, 1, 2) parietal lobe Somatotropic representation of the body Posterior parietal association cortex; Just posterior and ventral to the primary somatosensory areas is the posterior parietal association cortex, including Brodmann areas 5, and 7. Lesions usually in the dominant hemisphere and which include areas 5 and 7 of the posterior parietal association areas often result in astereognosis (inability to recognize objects by touch). There is no loss of tactile or proprioceptive sensation; rather, it is the integration of visual and somatosensory information that is impaired. Astereognosis is more common after left hemisphere damage than in right hemisphere damage and usually confined to the contralateral side of the body. STEREOGNOSIS Astereognosis (A=without, stereos=solid, gnosis=knowledge, put them all together it indicates= without knowledge of solids): It indicates impaired recognition of shape, forms and texture. Astereognosis is associated with lesions of the parietal lobe or dorsal column or parieto-temporo-occipital lobe (posterior association areas) of the cerebral cortex Agraphesthesia: unable to tell the number mapped on his/her palm. 6
GRAPHESTHESIA Abarognosis: impaired recognition of weight of the objects. Cortical lesions do not abolish somatic sensations. Proprioception & fine touch are most affected, temperature less & pain is the least affected by cortical lesions. Upon recovery, pain sensibility returns first then temperature & finally proprioception & fine touch. Asomatognosia and neglect; The integration of visual and somatosensory information is important for the formation of the "body image" and awareness of the body and its position in space. Widespread lesions in areas 7, 39, and 40 in the nondominant right parietal lobe may result in unawareness or neglect of the contralateral half of the body and asomatognosia. Although somatic sensation is intact, the patients ignore half of their body and may fail to dress, undress, or wash the affected (left) side. Patients will have no visual field defects, so they can see, but deny the existence of things in the left visual field. Asking them to bisect a horizontal line produces a point well to the right of true center. If asked to draw a clock face from memory (Clock drawing test), they will draw only numbers on the right side, ignoring those on the left. The patients may deny that the left arm or leg belongs to them when the affected limb passively brought into their field of vision (asomatognosia). Patients may also deny their deficit, an (anosognosia). Plasticity of the Brain: If a digit is amputated the cortical representation of neighboring digits spreads into the cortical area of the amputated finger. Also if cortical area representing a digit is removed, the somatosensory map of the digit moves to the surrounding cortex. So there is always plasticity to compensate for the loss in brain. 7
Figure 4. Unilateral neglect during clock drawing. The example is shown above and the patient's copy to the right. Not uncommonly, patients with left neglect sketch the entire circle and write the numerals 12, 3, 6, and 9 at their correct locations. The patient was satisfied that she had sketched the entire clock face shown to her. She acknowledged her omissions when they were indicated to her. Note the bunching of numerals on the right side, another characteristic of clock drawing by patients with neglect. Figure 5. Unilateral neglect when copying a scene, executed by the same patient from figure 5. Before she started copying, she was asked what she saw. She said, "A tree, a house, and a fence." After she believed that she had copied the entire picture, she was asked again what she saw in the original picture: "A tree and a house." Note not only the absence of figures from the left side of the scene, but also that only half the tree was drawn, thus demonstrating two different kinds of neglect on drawing tasks (i.e., environment-based neglect and object-based neglect). The distortion of elements in drawings (constructional apraxia), as shown here, is also common in patients with unilateral neglect Characteristics of signal transmission in the Dorsal Column: 1. At each stage of DC - ML system divergence occurs. 2. Two point discrimination: it is the minimal distance by which 2 touch stimuli must be separated to be perceived as separate. Points on back must be separated 30-70 mm to be recognized as 2 stimuli. While on fingertips 1-2 mm separation is enough for the brain to perceive them as 2 stimuli. The lateral inhibition in this tract increases the degree of contrast in the perceived spatial pattern. 8
3. Lateral inhibition occurs at each synaptic level (Medulla, Thalamus, &Cortex). 4. Transmission of vibration sense: Pacinian corpuscle signals vibration from 30-800 cycles / sec. & transmit their signals through Aβ nerve fibers. Low frequency vibration less than 200 cycles / sec. stimulate mainly Meissner's corpuscles. Vibration senses are carried through dorsal column only & for this reason it is a good diagnostic tool to test for the integrity of Dorsal Column. Vibration sense is the first sensation to be lost in diabetic patients. 5. Judgment of stimulus intensity in brain depends on the greater the background sensory intensity the greater an additional change must be for the psyche to detect the change (Weber - Fechner Principle). Interpreted signal strength = log (Stimulus) + constant Diseases of dorsal column; Tabes dorsalis (Dorsal wasting) It is caused by bilateral degeneration of the dorsal roots and dorsal columns. The slowly progressive degeneration of the spinal cord occurs as a result of an untreated syphilis infection in the tertiary (third) phase, a decade or more after originally contracting the infection. Syphilis is a sexually transmitted disease caused by bacteria named Treponema pallidum. There may be impaired vibration and position sense, 9
astereognosis, paroxysmal pains (irregular severe sharp stabbing pains usually in the lower limb, chest, or abdomen, caused by dorsal root involvement), and ataxia (sensory ataxia, and positive Romberg s test), as well as diminished stretch reflexes or incontinence. Owing to the loss of proprioceptive pathways, individuals with tabes dorsalis are unsure of where the ground is and walk with a characteristic and almost diagnostic "high step stride" They may also present with abnormal pupillary responses, pupils that accommodate but do not constrict in response to light (Argyll Robertson pupils). The disease is more frequent in males than in females. Onset is commonly during mid-life. The incidence of tabes dorsalis is rising, in part due to coassociated HIV infection. Penicillin, administered intravenously, is the treatment of choice. 2. Subacute combined degeneration of the spinal cord; It is caused by vitamin B12 deficiency sometimes related to pernicious anemia. Subacute combined degeneration is characterized by patchy losses of myelin in the dorsal columns and lateral corticospinal tracts, resulting in a bilateral spastic paresis and a bilateral alteration of touch, vibration, and pressure sensations below the lesion sites. Myelin in both CNS and PNS is affected (primarily affects the spinal cord, but it can also damage the brain, and the peripheral nerves). At first, the disease damages the myelin sheath; it later affects the entire nerve cell. How a lack of vitamin B12 damages nerves is unclear. However, experts believe the lack of this vitamin causes abnormal fatty acids to form around cells and nerves. You have a higher risk for this condition if you cannot absorb vitamin B12 from the intestine, (Pernicious anemia, Crohn's disease, Malabsorptive conditions, or after gastro-intestinal surgery), also in strict vegetarian diet or a poor diet due to factors such as aging or alcoholism. The proprioceptive system: The proprioceptive system arises from primarily the A β afferents entering the spinal cord. These are the afferents from muscle spindles, Golgi tendon organs, and joint receptors. The axons travel for a little while with the discriminative touch system, in the posterior columns. Within a few segments, however, the proprioceptive information slips out of the dorsal white matter and synapses. After synapsing it ascends without crossing to the cerebellum. Exactly where the axons synapse depends upon whether they originated in the legs or the arms. Leg fibers enter the cord at sacral or lumbar levels, ascend to the upper lumbar segments, and synapse in a medial nucleus called Clarke's nucleus (or nucleus dorsalis). The secondary afferents then enter the dorsal spinocerebellar tract on the lateral edge of the cord. 10
Fibers from the arm enter at cervical levels and ascend to the caudal medulla. Once there they synapse in a nucleus called the external cuneate (or lateral cuneate) nucleus, and the secondary axons join the leg information in the dorsal spinocerebellar tract. The spinocerebellar tract stays on the lateral margin of the brainstem all the way up the medulla. Just before reaching the pons, it is joined by a large projection from the inferior olive. These axons together make up the bulk of the inferior cerebellar peduncle, which grows right out of the lateral medulla and enters the cerebellum. The figures above outline the course of the dorsal spinocerebellar tract. Surely, there must be a ventral spinocerebellar tract? Naturally, there is, and it travels in approximately the same place - the lateral margin of the spinal cord, just ventral to the dorsal spinocerebellar tract. The two cannot be distinguished in a normal myelin stain. The ventral spinocerebellar tract seems to defy the ipsilaterality of the cerebellum, because the fibers entering it in the spinal cord actually cross on their way into the tract. However, they (somewhat inefficiently) cross back before entering the cerebellum. Therefore the cerebellum still gets information from the ipsilateral body. 11
Clinical correlate: Lesions that affect only the spinocerebellar tracts are uncommon, but there are a group of hereditary diseases in which degeneration of spinocerebellar pathways is a prominent feature. The most common of these is Friedreich Ataxia, which is usually inherited as an autosomal recessive trait. The spinocerebellar tracts, dorsal column, corticospinal tracts, and cerebellum may be involved. Ataxia of gait is the most common initial symptom of this disease. Peripheral receptors: The proprioceptive sensation relies on receptors in muscles and joints. The muscle spindle is the major stretch receptor within muscles. There are also Golgi tendon organs and joint afferents to monitor stresses and forces at the tendons and joints. Proprioceptive sense (Position sense) is of two types Static position sense, which means conscious perception of the orientation of different parts of the body with respect to each other. Dynamic proprioception, which indicates the rate of movement or kinesthesia. In fingers, proprioception is detected mainly by skin receptors, while in large joints deep receptors are more important in detecting proprioception. Pacinian corpuscle & muscle spindle are the main receptors responsible for detecting rate of movements (Dynamic proprioception). Axon diameters: Sensory axons can be classified according to diameter and therefore conduction velocity. The largest and fastest axons are called Aά, and include some of the proprioceptive neurons, such as the stretch receptor. The second largest group is called Aβ, which includes all of the discriminative touch receptors. A note about generalizations: There is actually a fair amount of mixing that goes on between the tracts. Some light touch information travels in the spinothalamic tract, so that lesioning the dorsal 12
columns will not completely knock out touch and pressure sensation. Some proprioception also travels in the dorsal columns, and follows the medial lemniscus all the way to the cortex, so there is conscious awareness of body position and movement. The pain and temperature system, although it does ascend to somatosensory cortex, also has multiple targets in the brainstem and other areas. sensory input from the face (discriminative touch, proprioception, and pain and temperature) all enters the brainstem via the trigeminal nerve. Just as in the spinal cord, these three modalities have different receptors, travel along different tracts, and have different targets in the brainstem. Once the pathways synapse in the brainstem, they join the pathways from the body on their way up to the thalamus. The trigeminal nucleus is huge - it stretches from midbrain to medulla. Discriminative touch: The large diameter (Ab) fibers enter directly into the main sensory nucleus of the trigeminal (V), also called the principal nucleus. Just like the somatosensory neurons of the body, they SYNAPSE, then CROSS. The secondary afferents can then join the medial lemniscus on its way to the thalamus. Proprioception: The proprioceptive axons in the trigeminal nerve are the stretch and tendon receptors from the muscles of mastication. (Recall that all of the muscles of facial expression are controlled by the facial nerve.) These axons coming from the face have a strange characteristic unique among primary somatosensory neurons: their cell bodies are inside the CNS. They are the only exception to the rule. Although their cells look similar to cells in the dorsal root ganglion, they are located inside the brainstem in a nucleus called the mesencephalic nucleus. The mesencephalic nucleus 13
is essentially a dorsal root ganglion that has been pushed into the CNS, so there are no synapses within it. The fibers enter the brainstem via a small branch of the trigeminal that bypasses the trigeminal ganglion, turn up towards the mesencephalic nucleus, pass by the cell body, and leave the nucleus immediately. Most then synapse in the nearby motor nucleus where they can initiate the stretch reflexes for the muscles of mastication. The stretch reflex in the face behaves exactly like that in the body, and tapping on the tendon of the masseter (for example) will produce a twitch. 14