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The knee-jerk reflex (patellar reflex) is an example of a stretch reflex (myotatic reflex). Stretch reflexes are monosynaptic reflexes happening in the spinal cord without involvement of the brain.
Does it mean that this reflex will continue to function in an unconscious person, e.g. under general anaesthesia? Does it depend on the "deepness" of anaesthesia? Does it depend on a specific drug? I would also be interested to know if spinal reflexes keep working in unconscious states such as e.g. alcohol poisoning or a knockout.
The issue is complicated. In general it depends on the specific spinal reflex and on the specific anaesthetic. But it seems that the modern general anaesthetics usually do NOT block monosynaptic spinal reflexes (such as knee-jerk).
Here are two figures from Baars et al. 2009 that show that propofol and sevoflurane strongly inhibit withdrawal reflex (spinal two-synaptic reflex) but have almost no effect on the H-reflex (spinal monosynaptic reflex closely connected to the stretch reflex):
See below for many more details. Disclaimer: I know very little about anaesthesia and am simply writing down what I found after a couple of days searching and reading.
As @AliceD wrote, withdrawal reflex (a two-synaptic spinal cord reflex) usually disappears under any anaesthesia and this disappearance is used as a clinical sign of anaesthesia being deep enough for the surgery. As an example, this handout on monitoring anaesthetic depth in rodents has the following entry on the list of criteria for surgical anesthesia:
Withdrawal reflexes are absent! Try at least 2 toes and the ears so that you are sure that this reflex is absent.
Knee-jerk reflex: early history
On the other hand, it is known from the XIX century that stretch reflexes such as knee-jerk (note that they are monosynaptic) are very persistent. They can be abolished under some drugs (such as e.g. chloroform and ether) that act directly on the spine, but keep working under others. I am quoting from three old papers on the topic (here and below emphasis is mine).
Horsley, 1883, Note on the patellar knee-jerk:
In 1881, while experimenting (on myself) with this gas [nitrous oxide] for a different purpose, it occurred to me to contrast the conditions of the superficial and deep "reflexes," taking the plantar reflex as an example of the former, and the patellar phenomenon to illustrate the latter. Being aware of the fact that deep chloroform-narcosis abolishes all the "reflexes," superficial and deep, and yet that with ether-narcosis, however deep, ankle-clonus frequently, appears, I was scarcely surprised to find that the knee-jerk persisted in the deepest anaesthesia from nitrous oxide, while the superficial reflexes all disappeared.
Sherrington, 1892, Notes on the arrangement of some motor fibres in the lumbo-sacral plexus (p 671):
With regard to the effect of anaesthetics on the "jerk," a better proof of the action of chloroform being rapid and direct on the nervous mechanisms of the cord itself could hardly be found than in the speedy abolition of the "jerk" by chloroform inhalation when the cord has been previously divided in the thoracic region.
Simpson & Herring, 1905, The effect of cold narcosis on reflex action in warm-blooded animals:
The knee-jerk is a very persistent phenomenon. It is known to disappear in deep anesthesia produced by ether or chloroform [Sherrington 1892]. [… ] The knee-jerk is as a rule easily elicited, and we find it present when all the reflexes have disappeared. [… ] The lower the temperature the smaller the jerk. [… ] In several animals that died at a low temperature the disappearance of the knee-jerk was simultaneous with death [… ] The lowest temperature at which we found the knee-jerk present was 15° C., and this was also the lowest temperature at which any of our animals were still alive. [… ] Pinching the skin does not provoke any response till the temperature is 25° C. [… ] We have compared these results with similar ones obtained from cats in recovery from deep ether anesthesia and find that the order of reappearance agrees very closely.
Modern studies in animals
Hara & Harris, 2002, The Anesthetic Mechanism of Urethane: The Effects on Neurotransmitter-Gated Ion Channels mention in the abstract that
Urethane is widely used as an anesthetic for animal studies because of its minimal effects on cardiovascular and respiratory systems and maintenance of spinal reflexes.
(they don't specify which reflexes specifically).
Ho & Waite, 2002, Effects of Different Anesthetics on the Paired-Pulse Depression of the H Reflex in Adult Rat study the effect of five different anaesthetics (ketamine, halothane, etomidate, saffan, and nembutal) on the Hoffman reflex (H-reflex), a monosynaptic reflex similar to the stretch reflex. They report that it keeps working under all five drugs, but the drugs modulate the decrease of the reflex under repeated stimulation (this decrease depends on the descending controls and is affected differently by different drugs):
The results suggest a preferential action of some anesthetics on descending pathways involved in reflex modulation [… ]
Strangely, Ho & Waite do not describe how anaesthesia affects the reflex strength following an unrepeated stimulation, but in any case it is clear the the reflex keeps functioning.
What about the anaesthetics widely used in humans, such as e.g. propofol? Matute et al., 2004, Effects of propofol and sevoflurane on the excitability of rat spinal motoneurones and nociceptive reflexes in vitro:
We used an isolated spinal cord in vitro preparation from rat pups and superfused the anaesthetics at known concentrations. [… ] Applied at anaesthetic concentrations, [… ] sevoflurane produced a large depressant effect on the monosynaptic reflex whereas propofol was ineffective. [… ] Sevoflurane produces large inhibitory effects on nociceptive and non-nociceptive reflexes which are likely to contribute to immobility during surgery. Compared with sevoflurane, propofol appears to have much weaker effects on spinal reflexes such as those recorded in an isolated preparation.
Kerz et al., 2001, Effects of Propofol on H-reflex in Humans:
Previous studies of motoneuron excitability using H-reflexes or F-waves during general anesthesia found significant depression after administration of halothane, enflurane, isoflurane, desflurane, or nitrous oxide. [… ]
Recommended propofol doses for induction and maintenance only had a transient effect on the H-reflex and were no longer demonstrable after 10 min of propofol anesthesia. [… ] Immobility during propofol anesthesia [… ] does not seem to be caused by a depression of spinal motoneuron circuit excitability.
So why is then the withdrawal reflex so easily abolished and the stretch reflex is so persistent (e.g. under propofol)? This does not seem to be well understood. Baars et al., 2009, Effects of Sevoflurane and Propofol on the Nociceptive Withdrawal Reflex and on the H Reflex write
Both H reflex and nociceptive withdrawal reflexes are reduced dose-dependently by propofol and sevoflurane in humans. [… ] We have shown a striking difference of the degree to which both reflexes are reduced by the two anesthetics. The relative reduction of the polysynaptic RIII reflex amplitude was more than four times higher than that of the H reflex. This difference can probably be attributed to the higher number of neurons interposed in the RIII reflex pathway in comparison to the H reflex.
Note that the last sentence is very vague; it says that the difference is "probably" due to monosynaptic vs. polysynaptic mechanisms of these two reflexes but does not offer any explanation. Withdrawal reflex is mediated by an excitatory interneuron and propofol acts on GABA (which is inhibitory transmitter), so it remains unclear. This study is from 2009 and I did not find anything relevant in the papers that cite it.
From an animal-experimentation perspective, the absence of functional reflex arches are often used to assess adequate anesthetic depth. For example, in rodents a toe-pinch is often used to assess whether the animal is sufficiently anesthetized to commence surgery. The absence of a withdrawal reflex marks the point to proceed after initiation of general anesthesia. Hence, in these cases, pain-induced muscle reflex arches are suppressed. Note it is a two-synaptic process (nociceptor to spinal chord, spinal chord to muscle).
I am not a surgeon. However, I might have some insight:
General anesthesia often (most of the time ?) include curare derivated drugs (such as pancuronium) that will effectively block any muscular response (by interfering in the neuromuscular junction: they block nicotinic Acetylcholine receptors). So this will effectively inhibate any reflex by blocking the final effector.
Spinal anesthesia might also inhibit reflex arc, for the same reasons, but only for a specific zone.
Other kind of anesthesia might be conservative regarding reflex arc.
You will find informations on wikipedia:
If you want me to give you a more elaborate answer, just say so, I will try to improve a little bit.
Many of us know about stretch reflexes from the doctor’s office, when a physician taps the tendon near our kneecap to elicit a quick knee extension. This procedure is used as a diagnostic tool to determine the integrity of the spinal cord and the extension response it elicits may seem otherwise useless. In fact, the tendon tap taps into one aspect of a critical building block of mammalian motor control, the stretch reflexes. Stretch reflexes are often thought to quickly resist unexpected changes in muscle length via a very simple circuit in the spinal cord, and this is one circuit that the tendon tap engages. It turns out, however, that stretch reflexes support a myriad of functions and are highly flexible. Under naturalistic conditions, stretch reflexes are shaped by peripheral physiology and engage neural circuits spanning the spinal cord, brainstem and cerebral cortex. In this Primer, we outline what is currently known about stretch reflex function and its underlying mechanisms, with a specific focus on how the cascade of nested responses collectively known as stretch reflexes interact with and build off of one another to support real-world motor behavior.
Reflex & Voluntary Control of Posture & Movement
Describe the elements of the stretch reflex and how the activity of γ-motor neurons alters the response to muscle stretch.
Describe the role of Golgi tendon organs in control of skeletal muscle.
Describe the elements of the withdrawal reflex.
Define spinal shock and describe the initial and long-term changes in spinal reflexes that follow transection of the spinal cord.
Describe how skilled movements are planned and carried out.
Compare the organization of the central pathways involved in the control of axial (posture) and distal (skilled movement, fine motor movements) muscles.
Define decerebrate and decorticate rigidity, and comment on the cause and physiologic significance of each.
Identify the components of the basal ganglia and the pathways that interconnect them, along with the neurotransmitters in each pathway.
Explain the pathophysiology and symptoms of Parkinson disease and Huntington disease.
Discuss the functions of the cerebellum and the neurologic abnormalities produced by diseases of this part of the brain.
Somatic motor activity depends ultimately on the pattern and rate of discharge of the spinal motor neurons and homologous neurons in the motor nuclei of the cranial nerves. These neurons, the final common paths to skeletal muscle, are bombarded by impulses from an immense array of descending pathways, other spinal neurons, and peripheral afferents. Some of these inputs end directly on α-motor neurons, but many exert their effects via interneurons or via γ-motor neurons to the muscle spindles and back through the Ia afferent fibers to the spinal cord. It is the integrated activity of these multiple inputs from spinal, medullary, midbrain, and cortical levels that regulates the posture of the body and makes coordinated movement possible.
The inputs converging on motor neurons have three functions: they bring about voluntary activity, they adjust body posture to provide a stable background for movement, and they coordinate the action of the various muscles to make movements smooth and precise. The patterns of voluntary activity are planned within the brain, and the commands are sent to the muscles primarily via the corticospinal and corticobulbar systems. Posture is continually adjusted not only before but also during movement by information carried in descending brainstem pathways and peripheral afferents. Movement is smoothed and coordinated by the medial and intermediate portions of the cerebellum (spinocerebellum) and its connections. The basal ganglia and the lateral portions of the cerebellum (cerebrocerebellum) are part of a feedback circuit to the premotor and motor cortex that is concerned with planning and organizing voluntary movement.
This chapter considers two types of motor output: reflex (involuntary) and voluntary. A subdivision of reflex responses includes some rhythmic movements such as swallowing, chewing, scratching, and walking, which are largely involuntary but subject to voluntary adjustment and control.
GENERAL PROPERTIES OF REFLEXES
The basic unit of integrated reflex activity is the reflex arc. This arc consists of a sense organ, an afferent neuron, one or more synapses within a central integrating station, an efferent neuron, and an effector. The afferent neurons enter via the dorsal roots or cranial nerves and have their cell bodies in the dorsal root ganglia or in the homologous ganglia of the cranial nerves. The efferent fibers leave via the ventral roots or corresponding motor cranial nerves.
Activity in the reflex arc starts in a sensory receptor with a receptor potential whose magnitude is proportional to the strength of the stimulus (Figure 12–1) . This generates all-or-none action potentials in the afferent nerve, the number of action potentials being proportional to the size of the receptor potential. In the central nervous system (CNS), the responses are again graded in terms of excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) at the synaptic junctions. All-or-none responses (action potentials) are generated in the efferent nerve. When these reach the effector, they again set up a graded response. When the effector is smooth muscle, responses summate to produce action potentials in the smooth muscle. In contrast, when the effector is skeletal muscle, the graded response is adequate to produce action potentials that bring about muscle contraction. The connection between the afferent and efferent neurons is in the CNS, and activity in the reflex arc is modified by the multiple inputs converging on the efferent neurons or at any synaptic station within the reflex arc.
The reflex arc. Note that at the receptor and in the CNS a nonpropagated graded response occurs that is proportional to the magnitude of the stimulus. The response at the neuromuscular junction is also graded, though under normal conditions it is always large enough to produce a response in skeletal muscle. On the other hand, in the portions of the arc specialized for transmission (afferent and efferent nerve fibers, muscle membrane), the responses are all-or-none action potentials.
The stimulus that triggers a reflex is generally very precise. This stimulus is called the adequate stimulus for the particular reflex. A dramatic example is the scratch reflex in the dog. This spinal reflex is adequately stimulated by multiple linear touch stimuli such as those produced by an insect crawling across the skin. The response is vigorous scratching of the area stimulated. If the multiple touch stimuli are widely separated or not in a line, the adequate stimulus is not produced and no scratching occurs. Fleas crawl, but they also jump from place to place. This jumping separates the touch stimuli so that an adequate stimulus for the scratch reflex is not produced.
Reflex activity is stereotyped and specific in that a particular stimulus elicits a particular response. The fact that reflex responses are stereotyped does not exclude the possibility of their being modified by experience. Reflexes are adaptable and can be modified to perform motor tasks and maintain balance. Descending inputs from higher brain regions play an important role in modulating and adapting spinal reflexes.
The α-motor neurons that supply the extrafusal fibers in skeletal muscles are the efferent side of many reflex arcs. All neural influences affecting muscular contraction ultimately funnel through them to the muscles, and they are therefore called the final common pathway. Numerous inputs converge on α-motor neurons. Indeed, the surface of the average motor neuron and its dendrites accommodates about 10,000 synaptic knobs. At least five inputs go from the same spinal segment to a typical spinal motor neuron. In addition to these, there are excitatory and inhibitory inputs, generally relayed via interneurons, from other levels of the spinal cord and multiple long-descending tracts from the brain. All of these pathways converge on and determine the activity in the final common pathways.
MONOSYNAPTIC REFLEXES: THE STRETCH REFLEX
The simplest reflex arc is one with a single synapse between the afferent and efferent neurons, and reflexes occurring in them are called monosynaptic reflexes. Reflex arcs in which interneurons are interposed between the afferent and efferent neurons are called polysynaptic reflexes. There can be anywhere from two to hundreds of synapses in a polysynaptic reflex arc.
When a skeletal muscle with an intact nerve supply is stretched, it contracts. This response is called the stretch reflex or myotatic reflex. The stimulus that initiates this reflex is stretch of the muscle, and the response is contraction of the muscle being stretched. The sense organ is a small encapsulated spindlelike or fusiform-shaped structure called the muscle spindle, located within the fleshy part of the muscle. The impulses originating from the spindle are transmitted to the CNS by fast sensory fibers that pass directly to the motor neurons that supply the same muscle. The neurotransmitter at the central synapse is glutamate. The stretch reflex is the best known and studied monosynaptic reflex and is typified by the knee jerk reflex (Clinical Box 12–1) .
CLINICAL BOX 12–1 Knee Jerk Reflex
Tapping the patellar tendon elicits the knee jerk, a stretch reflex of the quadriceps femoris muscle, because the tap on the tendon stretches the muscle. A similar contraction is observed if the quadriceps is stretched manually. Stretch reflexes can be elicited from most of the large muscles of the body. Tapping on the tendon of the triceps brachii, for example, causes an extensor response at the elbow as a result of reflex contraction of the triceps tapping on the Achilles tendon causes an ankle jerk due to reflex contraction of the gastrocnemius and tapping on the side of the face causes a stretch reflex in the masseter. The knee jerk reflex is an example of a deep tendon reflex (DTR) in a neurologic exam and is graded on the following scale: 0 (absent), 1+ (hypoactive), 2+ (brisk, normal), 3+ (hyperactive without clonus), 4+ (hyperactive with mild clonus), and 5+ (hyperactive with sustained clonus). Absence of the knee jerk can signify an abnormality anywhere within the reflex arc, including the muscle spindle, the Ia afferent nerve fibers, or the motor neurons to the quadriceps muscle. The most common cause is a peripheral neuropathy from such things as diabetes, alcoholism, and toxins. A hyperactive reflex can signify an interruption of corticospinal and other descending pathways that suppress the activity in the reflex arc.
STRUCTURE OF MUSCLE SPINDLES
Each muscle spindle has three essential elements: (1) a group of specialized intrafusal muscle fibers with contractile polar ends and a noncontractile center, (2) large diameter myelinated afferent nerves (types Ia and II) originating in the central portion of the intrafusal fibers, and (3) small diameter myelinated efferent nerves supplying the polar contractile regions of the intrafusal fibers (Figure 12–2A) . It is important to understand the relationship of these elements to each other and to the muscle itself to appreciate the role of this sense organ in signaling changes in the length of the muscle in which it is located. Changes in muscle length are associated with changes in joint angle thus muscle spindles provide information on position (ie, proprioception ).
Mammalian muscle spindle. A) Diagrammatic representation of the main components of mammalian muscle spindle including intrafusal muscle fibers, afferent sensory fiber endings, and efferent motor fibers (γ-motor neurons). B) Three types of intrafusal muscle fibers: dynamic nuclear bag, static nuclear bag, and nuclear chain fibers. A single Ia afferent fiber innervates all three types of fibers to form a primary sensory ending. A group II sensory fiber innervates nuclear chain and static bag fibers to form a secondary sensory ending. Dynamic γ-motor neurons innervate dynamic bag fibers static γ-motor neurons innervate combinations of chain and static bag fibers. C) Comparison of discharge pattern of Ia afferent activity during stretch alone and during stimulation of static or dynamic γ-motor neurons. Without γ-stimulation, Ia fibers show a small dynamic response to muscle stretch and a modest increase in steady-state firing. When static γ-motor neurons are activated, the steady-state response increases and the dynamic response decreases. When dynamic γ-motor neurons are activated, the dynamic response is markedly increased but the steady-state response gradually returns to its original level. (Reproduced with permission from Gray H: Gray’s Anatomy: The Anatomical Basis of Clinical Practice, 40th ed. St. Louis, MO: Churchill Livingstone/Elsevier 2009.)
The intrafusal fibers are positioned in parallel to the extrafusal fibers (the regular contractile units of the muscle) with the ends of the spindle capsule attached to the tendons at either end of the muscle. Intrafusal fibers do not contribute to the overall contractile force of the muscle, but rather serve a pure sensory function. There are two types of intrafusal fibers in mammalian muscle spindles. The first type contains many nuclei in a dilated central area and is called a nuclear bag fiber (Figure 12–2B) . There are two subtypes of nuclear bag fibers, dynamic and static. The second intrafusal fiber type, the nuclear chain fiber, is thinner and shorter and lacks a definite bag. Typically, each muscle spindle contains two or three nuclear bag fibers and about five nuclear chain fibers.
There are two kinds of sensory endings in each spindle, a single primary (group Ia) ending and up to eight secondary (group II) endings (Figure 12–2B). The Ia afferent fiber wraps around the center of the dynamic and static nuclear bag fibers and nuclear chain fibers. Group II sensory fibers are located adjacent to the centers of the static nuclear bag and nuclear chain fibers these fibers do not innervate the dynamic nuclear bag fibers. Ia afferents are very sensitive to the velocity of the change in muscle length during a stretch (dynamic response) thus they provide information about the speed of movements and allow for quick corrective movements. The steady-state (tonic) activity of group Ia and II afferents provide information on steady-state length of the muscle (static response). The top trace in Figure 12–2C shows the dynamic and static components of activity in a Ia afferent during muscle stretch. Note that they discharge most rapidly while the muscle is being stretched (shaded area of graphs) and less rapidly during sustained stretch.
The spindles have a motor nerve supply of their own. These nerves are 3–6 μm in diameter, constitute about 30% of the fibers in the ventral roots, and are called γ-motor neurons. There are two types of γ-motor neurons: dynamic, which supply the dynamic nuclear bag fibers and static, which supply the static nuclear bag fibers and the nuclear chain fibers. Activation of dynamic γ-motor neurons increases the dynamic sensitivity of the group Ia endings. Activation of the static γ-motor neurons increases the tonic level of activity in both group Ia and II endings, decreases the dynamic sensitivity of group Ia afferents, and can prevent silencing of Ia afferents during muscle stretch (Figure 12–2C).
CENTRAL CONNECTIONS OF AFFERENT FIBERS
Ia fibers end directly on motor neurons supplying the extrafusal fibers of the same muscle (Figure 12–3) . The time between the application of the stimulus and the response is called the reaction time. In humans, the reaction time for a stretch reflex such as the knee jerk is 19–24 ms. Weak stimulation of the sensory nerve from the muscle, known to stimulate only Ia fibers, causes a contractile response with a similar latency. Because the conduction velocities of the afferent and efferent fiber types are known and the distance from the muscle to the spinal cord can be measured, it is possible to calculate how much of the reaction time was taken up by conduction to and from the spinal cord. When this value is subtracted from the reaction time, the remainder, called the central delay, is the time taken for the reflex activity to traverse the spinal cord. The central delay for the knee jerk reflex is 0.6–0.9 ms. Because the minimum synaptic delay is 0.5 ms, only one synapse could have been traversed.
Diagram illustrating the pathways responsible for the stretch reflex and the inverse stretch reflex. Stretch stimulates the muscle spindle, which activates Ia fibers that excite the motor neuron. Stretch also stimulates the Golgi tendon organ, which activates Ib fibers that excite an interneuron that releases the inhibitory mediator glycine. With strong stretch, the resulting hyperpolarization of the motor neuron is so great that it stops discharging.
FUNCTION OF MUSCLE SPINDLES
When the muscle spindle is stretched, its sensory endings are distorted and receptor potentials are generated. These in turn set up action potentials in the sensory fibers at a frequency proportional to the degree of stretching. Because the spindle is in parallel with the extrafusal fibers, when the muscle is passively stretched, the spindles are also stretched, referred to as “loading the spindle.” This initiates reflex contraction of the extrafusal fibers in the muscle. On the other hand, the spindle afferents characteristically stop firing when the muscle is made to contract by electrical stimulation of the α-motor neurons to the extrafusal fibers because the muscle shortens while the spindle is unloaded (Figure 12–4) .
Effect of various conditions on muscle spindle discharge. When the whole muscle is stretched, the muscle spindle is also stretched and its sensory endings are activated at a frequency proportional to the degree of stretching (“loading the spindle”). Spindle afferents stop firing when the muscle contracts (“unloading the spindle”). Stimulation of γ-motor neurons cause the contractile ends of the intrafusal fibers to shorten. This stretches the nuclear bag region, initiating impulses in sensory fibers. If the whole muscle is stretched during stimulation of the γ-motor neurons, the rate of discharge in sensory fibers is further increased.
The muscle spindle and its reflex connections constitute a feedback device that operates to maintain muscle length. If the muscle is stretched, spindle discharge increases and reflex shortening is produced. If the muscle is shortened without a change in γ-motor neuron discharge, spindle afferent activity decreases and the muscle relaxes.
Dynamic and static responses of muscle spindle afferents influence physiologic tremor. The response of the Ia sensory fiber endings to the dynamic (phasic) as well as the static events in the muscle is important because the prompt, marked phasic response helps dampen oscillations caused by conduction delays in the feedback loop regulating muscle length. Normally a small oscillation occurs in this feedback loop. This physiologic tremor has low amplitude (barely visible to the naked eye) and a frequency of approximately 10 Hz. Physiologic tremor is a normal phenomenon that affects everyone while maintaining posture or during movements. However, the tremor would be more prominent if it were not for the sensitivity of the spindle to velocity of stretch. It can become exaggerated in some situations such as when we are anxious or tired or because of drug toxicity. Numerous factors contribute to the genesis of physiologic tremor. It is likely dependent on not only central (inferior olive) sources but also peripheral factors including motor unit firing rates, reflexes, and mechanical resonance.
EFFECTS OF γ-MOTOR NEURON DISCHARGE
Stimulation of γ-motor neurons produces a very different picture from that produced by stimulation of the α-motor neurons. Stimulation of γ-motor neurons does not lead directly to detectable contraction of the muscles because the intrafusal fibers are not strong enough or plentiful enough to cause shortening. However, stimulation does cause the contractile ends of the intrafusal fibers to shorten and therefore stretches the nuclear bag portion of the spindles, deforming the endings, and initiating impulses in the Ia fibers (Figure 12–4). This in turn can lead to reflex contraction of the muscle. Thus, muscles can be made to contract via stimulation of the α-motor neurons that innervate the extrafusal fibers or the γ-motor neurons that initiate contraction indirectly via the stretch reflex.
If the whole muscle is stretched during stimulation of the γ-motor neurons, the rate of discharge in the Ia fibers is further increased (Figure 12–4). Increased γ-motor neuron activity thus increases spindle sensitivity during stretch.
In response to descending excitatory input to spinal motor circuits, both α- and γ-motor neurons are activated. Because of this “α–γ coactivation,” intrafusal and extrafusal fibers shorten together, and spindle afferent activity can occur throughout the period of muscle contraction. In this way, the spindle remains capable of responding to stretch and reflexively adjusting α-motor neuron discharge.
CONTROL OF γ-MOTOR NEURON DISCHARGE
The γ-motor neurons are regulated to a large degree by descending tracts from a number of areas in the brain that also control α-motor neurons (described below). Via these pathways, the sensitivity of the muscle spindles and hence the threshold of the stretch reflexes in various parts of the body can be adjusted and shifted to meet the needs of postural control.
Other factors also influence γ-motor neuron discharge. Anxiety causes an increased discharge, a fact that probably explains the hyperactive tendon reflexes sometimes seen in anxious patients. In addition, unexpected movement is associated with a greater efferent discharge. Stimulation of the skin, especially by noxious agents, increases γ-motor neuron discharge to ipsilateral flexor muscle spindles while decreasing that to extensors and produces the opposite pattern in the opposite limb. It is well known that trying to pull the hands apart when the flexed fingers are hooked together facilitates the knee jerk reflex (Jendrassik maneuver), and this may also be due to increased γ-motor neuron discharge initiated by afferent impulses from the hands.
When a stretch reflex occurs, the muscles that antagonize the action of the muscle involved (antagonists) relax. This phenomenon is said to be due to reciprocal innervation. Impulses in the Ia fibers from the muscle spindles of the protagonist muscle cause postsynaptic inhibition of the motor neurons to the antagonists. The pathway mediating this effect is bisynaptic. A collateral from each Ia fiber passes in the spinal cord to an inhibitory interneuron that synapses on a motor neuron supplying the antagonist muscles. This example of postsynaptic inhibition is discussed in Chapter 6, and the pathway is illustrated in Figure 6–6.
INVERSE STRETCH REFLEX
Up to a point, the harder a muscle is stretched, the stronger is the reflex contraction. However, when the tension becomes great enough, contraction suddenly ceases and the muscle relaxes. This relaxation in response to strong stretch is called the inverse stretch reflex. The receptor for the inverse stretch reflex is in the Golgi tendon organ (Figure 12–5) . This organ consists of a netlike collection of knobby nerve endings among the fascicles of a tendon. There are 3–25 muscle fibers per tendon organ. The fibers from the Golgi tendon organs make up the Ib group of myelinated, rapidly conducting sensory nerve fibers. Stimulation of these Ib fibers leads to the production of IPSPs on the motor neurons that supply the muscle from which the fibers arise. The Ib fibers end in the spinal cord on inhibitory interneurons that in turn terminate directly on the motor neurons (Figure 12–3). They also make excitatory connections with motor neurons supplying antagonists to the muscle.
Golgi tendon organ. This organ is the receptor for the inverse stretch reflex and consists of a netlike collection of knobby nerve endings among the fascicles of a tendon. The innervation is the Ib group of myelinated, rapidly conducting sensory nerve fibers. (Reproduced with permission from Gray H: Gray’s Anatomy: The Anatomical Basis of Clinical Practice, 40th ed. St. Louis, MO: Churchill Livingstone/Elsevier 2009.)
A characteristic of states in which increased γ-motor neuron discharge is present is clonus. This neurologic sign is the occurrence of regular, repetitive, rhythmic contractions of a muscle subjected to sudden, maintained stretch. Only sustained clonus with five or more beats is considered abnormal. Ankle clonus is a typical example. This is initiated by brisk, maintained dorsiflexion of the foot, and the response is rhythmic plantar flexion at the ankle. The stretch reflex–inverse stretch reflex sequence may contribute to this response. However, it can occur on the basis of synchronized motor neuron discharge without Golgi tendon organ discharge. The spindles of the tested muscle are hyperactive, and the burst of impulses from them discharges all the motor neurons supplying the muscle at once. The consequent muscle contraction stops spindle discharge. However, the stretch has been maintained, and as soon as the muscle relaxes it is again stretched and the spindles stimulated. There are numerous causes of abnormal clonus including traumatic brain injury, brain tumors, strokes, and multiple sclerosis. Clonus may also occur in spinal cord injury that disrupts the descending cortical input to a spinal glycinergic inhibitory interneuron called the Renshaw cell. This cell receives excitatory input from α-motor neurons via axon collaterals (and in turn it inhibits the same α-motor neuron). In addition, cortical fibers activating ankle flexors contact Renshaw cells (as well as type Ia inhibitory interneurons) that inhibit the antagonistic ankle extensors. This circuitry prevents reflex stimulation of the extensors when flexors are active. Therefore, when the descending cortical fibers are damaged (upper motor neuron lesion), the inhibition of antagonists is absent. The result is repetitive, sequential contraction of ankle flexors and extensors (clonus). Clonus may be seen in patients with amyotrophic lateral sclerosis, stroke, multiple sclerosis, spinal cord damage, epilepsy, liver or kidney failure, and hepatic encephalopathy.
Treatment of clonus often centers on its underlying cause. For some individuals, physical therapy that includes stretching exercises can reduce episodes of clonus. Immunosuppressants (eg, azathioprine and corticosteroids ), anticonvulsants (eg, primidone and levetiracetam), and tranquilizers (eg, clonazepam) have been shown to be beneficial in the treatment of clonus. Botulinum toxin has also been used to block the release of acetylcholine in the muscle, which triggers the rhythmic muscle contractions that are characteristic of clonus.
Because the Golgi tendon organs, unlike the spindles, are in series with the muscle fibers, they are stimulated by both passive stretch and active contraction of the muscle. The threshold of the Golgi tendon organs is low. The degree of stimulation by passive stretch is not great because the more elastic muscle fibers take up much of the stretch, and this is why it takes a strong stretch to produce relaxation. However, discharge is regularly produced by contraction of the muscle, and the Golgi tendon organ thus functions as a transducer in a feedback circuit that regulates muscle force in a manner analogous to the spindle feedback circuit that regulates muscle length.
The importance of the primary endings in the spindles and the Golgi tendon organs in regulating the velocity of the muscle contraction, muscle length, and muscle force is illustrated by the fact that section of the afferent nerves to an arm causes the limb to hang loosely in a semiparalyzed state. The interaction of spindle discharge, tendon organ discharge, and reciprocal innervation determines the rate of discharge of α-motor neurons (Clinical Box 12–2) .
The resistance of a muscle to stretch is often referred to as its tone or tonus. If the motor nerve to a muscle is severed, the muscle offers very little resistance and is said to be flaccid. A hypertonic (spastic) muscle is one in which the resistance to stretch is high because of hyperactive stretch reflexes. Somewhere between the states of flaccidity and spasticity is the ill-defined area of normal tone. The muscles are generally hypotonic when the rate of γ-motor neuron discharge is low and hypertonic when it is high.
When the muscles are hypertonic, the sequence of moderate stretch → muscle contraction, strong stretch → muscle relaxation is clearly seen. Passive flexion of the elbow, for example, meets immediate resistance as a result of the stretch reflex in the triceps muscle. Further stretch activates the inverse stretch reflex. The resistance to flexion suddenly collapses, and the arm flexes. Continued passive flexion stretches the muscle again, and the sequence may be repeated. This sequence of resistance followed by a sudden decrease in resistance when a limb is moved passively is known as the clasp-knife effect because of its resemblance to the closing of a pocket knife. It is also known as the lengthening reaction because it is the response of a spastic muscle to lengthening.
POLYSYNAPTIC REFLEXES: THE WITHDRAWAL REFLEX
Polysynaptic reflex paths branch in a complex manner. The number of synapses in each of their branches varies. Because of the synaptic delay at each synapse, activity in the branches with fewer synapses reaches the motor neurons first, followed by activity in the longer pathways. This causes prolonged bombardment of the motor neurons from a single stimulus and consequently prolonged responses. Furthermore, some of the branch pathways turn back on themselves, permitting activity to reverberate until it becomes unable to cause a propagated transsynaptic response and dies out. Such reverberating circuits are common in the brain and spinal cord.
The withdrawal reflex is a typical polysynaptic reflex that occurs in response to a noxious stimulus to the skin or subcutaneous tissues and muscle. The response is flexor muscle contraction and inhibition of extensor muscles, so that the body part stimulated is flexed and withdrawn from the stimulus. When a strong stimulus is applied to a limb, the response includes not only flexion and withdrawal of that limb but also extension of the opposite limb. This crossed extensor response is properly part of the withdrawal reflex. Strong stimuli can generate activity in the interneuron pool that spreads to all four extremities. This spread of excitatory impulses up and down the spinal cord to more and more motor neurons is called irradiation of the stimulus, and the increase in the number of active motor units is called recruitment of motor units.
IMPORTANCE OF THE WITHDRAWAL REFLEX
Flexor responses can be produced by innocuous stimulation of the skin or by stretch of the muscle, but strong flexor responses with withdrawal are initiated only by stimuli that are noxious or at least potentially harmful (ie, nociceptive stimuli ). The withdrawal reflex serves a protective function as flexion of the stimulated limb gets it away from the source of irritation, and extension of the other limb supports the body. The pattern assumed by all four extremities puts one in position to escape from the offending stimulus. Withdrawal reflexes are prepotent that is, they preempt the spinal pathways from any other reflex activity taking place at the moment.
Many of the characteristics of polysynaptic reflexes can be demonstrated by studying the withdrawal reflex. A weak noxious stimulus to one foot evokes a minimal flexion response stronger stimuli produce greater and greater flexion as the stimulus irradiates to more and more of the motor neuron pool supplying the muscles of the limb. Stronger stimuli also cause a more prolonged response. A weak stimulus causes one quick flexion movement a strong stimulus causes prolonged flexion and sometimes a series of flexion movements. This prolonged response is due to prolonged, repeated firing of the motor neurons. The repeated firing is called after-discharge and is due to continued bombardment of motor neurons by impulses arriving by complicated and circuitous polysynaptic paths.
As the strength of a noxious stimulus is increased, the reaction time is shortened. Spatial and temporal facilitation occurs at synapses in the polysynaptic pathway. Stronger stimuli produce more action potentials per second in the active branches and cause more branches to become active summation of the EPSPs to the threshold level for action potential generation occurs more rapidly.
FRACTIONATION & OCCLUSION
Another characteristic of the withdrawal response is the fact that supramaximal stimulation of any of the sensory nerves from a limb never produces as strong a contraction of the flexor muscles as that elicited by direct electrical stimulation of the muscles themselves. This indicates that the afferent inputs fractionate the motor neuron pool that is, each input goes to only part of the motor neuron pool for the flexors of that particular extremity. On the other hand, if all the sensory inputs are dissected out and stimulated one after the other, the sum of the tension developed by stimulation of each is greater than that produced by direct electrical stimulation of the muscle or stimulation of all inputs at once. This indicates that the various afferent inputs share some of the motor neurons and that occlusion occurs when all inputs are stimulated at once.
SPINAL INTEGRATION OF REFLEXES
The responses of animals and humans to spinal cord injury (SCI) illustrate the integration of reflexes at the spinal level. The deficits seen after SCI vary, of course, depending on the level of the injury. Clinical Box 12–3 provides information on long-term problems related to SCI and recent advancements in treatment options.
CLINICAL BOX 12–3 Spinal Cord Injury
It has been estimated that the worldwide annual incidence of sustaining spinal cord injury (SCI) is between 10 and 83 per million of the population. Leading causes are vehicular accidents, violence, and sports injuries. The mean age of patients who sustain an SCI is 33 years old, and men outnumber women with a nearly 4:1 ratio. Approximately 52% of SCI cases result in quadriplegia and about 42% lead to paraplegia. In quadriplegic persons, the threshold of the withdrawal reflex is very low even minor noxious stimuli may cause not only prolonged withdrawal of one extremity but marked flexion–extension patterns in the other three limbs. Stretch reflexes are also hyperactive. Afferent stimuli irradiate from one reflex center to another after SCI. When even a relatively minor noxious stimulus is applied to the skin, it may activate autonomic neurons and produce evacuation of the bladder and rectum, sweating, pallor, and blood pressure swings in addition to the withdrawal response. This distressing mass reflex can however sometimes be used to give paraplegic patients a degree of bladder and bowel control. They can be trained to initiate urination and defecation by stroking or pinching their thighs, thus producing an intentional mass reflex. If the cord section is incomplete, the flexor spasms initiated by noxious stimuli can be associated with bursts of pain that are particularly bothersome. They can be treated with considerable success with baclofen, a GABA B receptor agonist that crosses the blood-brain barrier and facilitates inhibition.
Treatment of SCI patients presents complex problems. Administration of corticosteroids such as methylprednisolone may have beneficial effects by fostering recovery and minimizing loss of function after SCI. They need to be given soon after the injury and then discontinued because of the well-established deleterious effects of long-term corticosteroid treatment. Their immediate value is likely due to reduction of the inflammatory response in the damaged tissue. Because SCI patients are immobile, a negative nitrogen balance develops and large amounts of body protein are catabolized. Their body weight compresses the circulation to the skin over bony prominences, causing formation of pressure ulcers. The ulcers heal poorly and are prone to infection because of body protein depletion. The tissues that are broken down include the protein matrix of bone and this, plus the immobilization, cause Ca 2+ to be released in large amounts, leading to hypercalcemia, hypercalciuria, and formation of calcium stones in the urinary tract. The combination of stones and bladder paralysis cause urinary stasis, which predisposes to urinary tract infection, the most common complication of SCI. The search continues for ways to get axons of neurons in the spinal cord to regenerate. Administration of neurotrophins shows some promise in experimental animals, and so does implantation of embryonic stem cells at the site of injury. Another possibility being explored is bypassing the site of SCI with brain-computer interface devices. However, these novel approaches are a long way from routine clinical use.
In all vertebrates, transection of the spinal cord is followed by a period of spinal shock during which all spinal reflex responses are profoundly depressed. Subsequently, reflex responses return and become hyperactive. The duration of spinal shock is proportional to the degree of encephalization of motor function in the various species. In frogs and rats it lasts for minutes in dogs and cats it lasts for 1–2 h in monkeys it lasts for days and in humans it usually lasts for a minimum of 2 weeks.
Cessation of tonic bombardment of spinal neurons by excitatory impulses in descending pathways (see below) undoubtedly plays a role in development of spinal shock. In addition, spinal inhibitory interneurons that normally are themselves inhibited may be released from this descending inhibition to become disinhibited. This, in turn, would inhibit motor neurons. The recovery of reflex excitability may be due to the development of denervation hypersensitivity to the mediators released by the remaining spinal excitatory endings. Another contributing factor may be sprouting of collaterals from existing neurons, with the formation of additional excitatory endings on interneurons and motor neurons.
The tendon organ consists simply of an afferent nerve fibre that terminates in a number of branches upon slips of tendon where the tendons join onto muscle fibres. By lying in series with muscle, the tendon organ is well placed to signal muscular tension. In fact, the afferent fibre of the tendon organ is sufficiently sensitive to generate a useful signal on the contraction of a single muscle fibre. In this way tendon organs provide a continuous flow of information on the level of muscular contraction.
In vertebrates the brain and spinal cord are both enclosed in the meninges.  The meninges provide a barrier to chemicals dissolved in the blood, protecting the brain from most neurotoxins commonly found in food. Within the meninges the brain and spinal cord are bathed in cerebral spinal fluid which replaces the body fluid found outside the cells of all bilateral animals.
In vertebrates the CNS is contained within the dorsal body cavity, with the brain is housed in the cranial cavity within the skull, and the spinal cord is housed in the spinal canal within the vertebrae.  Within the CNS, the interneuronal space is filled with a large amount of supporting non-nervous cells called neuroglia or glia from the Greek for "glue". 
In vertebrates the CNS also includes the retina  and the optic nerve (cranial nerve II),   as well as the olfactory nerves and olfactory epithelium.  As parts of the CNS, they connect directly to brain neurons without intermediate ganglia. The olfactory epithelium is the only central nervous tissue outside the meninges in direct contact with the environment, which opens up a pathway for therapeutic agents which cannot otherwise cross the meninges barrier. 
The CNS consists of the two major structures: the brain and spinal cord. The brain is encased in the skull, and protected by the cranium.  The spinal cord is continuous with the brain and lies caudally to the brain.  It is protected by the vertebrae.  The spinal cord reaches from the base of the skull, continues through  or starting below  the foramen magnum,  and terminates roughly level with the first or second lumbar vertebra,   occupying the upper sections of the vertebral canal. 
White and gray matter Edit
Microscopically, there are differences between the neurons and tissue of the CNS and the peripheral nervous system (PNS).  The CNS is composed of white and gray matter.  This can also be seen macroscopically on brain tissue. The white matter consists of axons and oligodendrocytes, while the gray matter consists of neurons and unmyelinated fibers. Both tissues include a number of glial cells (although the white matter contains more), which are often referred to as supporting cells of the CNS. Different forms of glial cells have different functions, some acting almost as scaffolding for neuroblasts to climb during neurogenesis such as bergmann glia, while others such as microglia are a specialized form of macrophage, involved in the immune system of the brain as well as the clearance of various metabolites from the brain tissue.  Astrocytes may be involved with both clearance of metabolites as well as transport of fuel and various beneficial substances to neurons from the capillaries of the brain. Upon CNS injury astrocytes will proliferate, causing gliosis, a form of neuronal scar tissue, lacking in functional neurons. 
The brain (cerebrum as well as midbrain and hindbrain) consists of a cortex, composed of neuron-bodies constituting gray matter, while internally there is more white matter that form tracts and commissures. Apart from cortical gray matter there is also subcortical gray matter making up a large number of different nuclei. 
Spinal cord Edit
From and to the spinal cord are projections of the peripheral nervous system in the form of spinal nerves (sometimes segmental nerves  ). The nerves connect the spinal cord to skin, joints, muscles etc. and allow for the transmission of efferent motor as well as afferent sensory signals and stimuli.  This allows for voluntary and involuntary motions of muscles, as well as the perception of senses. All in all 31 spinal nerves project from the brain stem,  some forming plexa as they branch out, such as the brachial plexa, sacral plexa etc.  Each spinal nerve will carry both sensory and motor signals, but the nerves synapse at different regions of the spinal cord, either from the periphery to sensory relay neurons that relay the information to the CNS or from the CNS to motor neurons, which relay the information out. 
The spinal cord relays information up to the brain through spinal tracts through the final common pathway  to the thalamus and ultimately to the cortex.
Schematic image showing the locations of a few tracts of the spinal cord.
Reflexes may also occur without engaging more than one neuron of the CNS as in the below example of a short reflex.
Cranial nerves Edit
Apart from the spinal cord, there are also peripheral nerves of the PNS that synapse through intermediaries or ganglia directly on the CNS. These 12 nerves exist in the head and neck region and are called cranial nerves. Cranial nerves bring information to the CNS to and from the face, as well as to certain muscles (such as the trapezius muscle, which is innervated by accessory nerves  as well as certain cervical spinal nerves). 
Two pairs of cranial nerves the olfactory nerves and the optic nerves  are often considered structures of the CNS. This is because they do not synapse first on peripheral ganglia, but directly on CNS neurons. The olfactory epithelium is significant in that it consists of CNS tissue expressed in direct contact to the environment, allowing for administration of certain pharmaceuticals and drugs. 
At the anterior end of the spinal cord lies the brain.  The brain makes up the largest portion of the CNS. It is often the main structure referred to when speaking of the nervous system in general. The brain is the major functional unit of the CNS. While the spinal cord has certain processing ability such as that of spinal locomotion and can process reflexes, the brain is the major processing unit of the nervous system.   [ citation needed ]
The brainstem consists of the medulla, the pons and the midbrain. The medulla can be referred to as an extension of the spinal cord, which both have similar organization and functional properties.  The tracts passing from the spinal cord to the brain pass through here. 
Regulatory functions of the medulla nuclei include control of blood pressure and breathing. Other nuclei are involved in balance, taste, hearing, and control of muscles of the face and neck. 
The next structure rostral to the medulla is the pons, which lies on the ventral anterior side of the brainstem. Nuclei in the pons include pontine nuclei which work with the cerebellum and transmit information between the cerebellum and the cerebral cortex.  In the dorsal posterior pons lie nuclei that are involved in the functions of breathing, sleep, and taste. 
The midbrain, or mesencephalon, is situated above and rostral to the pons. It includes nuclei linking distinct parts of the motor system, including the cerebellum, the basal ganglia and both cerebral hemispheres, among others. Additionally, parts of the visual and auditory systems are located in the midbrain, including control of automatic eye movements. 
The brainstem at large provides entry and exit to the brain for a number of pathways for motor and autonomic control of the face and neck through cranial nerves,  Autonomic control of the organs is mediated by the tenth cranial nerve.  A large portion of the brainstem is involved in such autonomic control of the body. Such functions may engage the heart, blood vessels, and pupils, among others. 
The brainstem also holds the reticular formation, a group of nuclei involved in both arousal and alertness. 
The cerebellum lies behind the pons. The cerebellum is composed of several dividing fissures and lobes. Its function includes the control of posture and the coordination of movements of parts of the body, including the eyes and head, as well as the limbs. Further, it is involved in motion that has been learned and perfected through practice, and it will adapt to new learned movements.  Despite its previous classification as a motor structure, the cerebellum also displays connections to areas of the cerebral cortex involved in language and cognition. These connections have been shown by the use of medical imaging techniques, such as functional MRI and Positron emission tomography. 
The body of the cerebellum holds more neurons than any other structure of the brain, including that of the larger cerebrum, but is also more extensively understood than other structures of the brain, as it includes fewer types of different neurons.  It handles and processes sensory stimuli, motor information, as well as balance information from the vestibular organ. 
The two structures of the diencephalon worth noting are the thalamus and the hypothalamus. The thalamus acts as a linkage between incoming pathways from the peripheral nervous system as well as the optical nerve (though it does not receive input from the olfactory nerve) to the cerebral hemispheres. Previously it was considered only a "relay station", but it is engaged in the sorting of information that will reach cerebral hemispheres (neocortex). 
Apart from its function of sorting information from the periphery, the thalamus also connects the cerebellum and basal ganglia with the cerebrum. In common with the aforementioned reticular system the thalamus is involved in wakefullness and consciousness, such as though the SCN. 
The hypothalamus engages in functions of a number of primitive emotions or feelings such as hunger, thirst and maternal bonding. This is regulated partly through control of secretion of hormones from the pituitary gland. Additionally the hypothalamus plays a role in motivation and many other behaviors of the individual. 
The cerebrum of cerebral hemispheres make up the largest visual portion of the human brain. Various structures combine to form the cerebral hemispheres, among others: the cortex, basal ganglia, amygdala and hippocampus. The hemispheres together control a large portion of the functions of the human brain such as emotion, memory, perception and motor functions. Apart from this the cerebral hemispheres stand for the cognitive capabilities of the brain. 
Connecting each of the hemispheres is the corpus callosum as well as several additional commissures.  One of the most important parts of the cerebral hemispheres is the cortex, made up of gray matter covering the surface of the brain. Functionally, the cerebral cortex is involved in planning and carrying out of everyday tasks. 
The hippocampus is involved in storage of memories, the amygdala plays a role in perception and communication of emotion, while the basal ganglia play a major role in the coordination of voluntary movement. 
Difference from the peripheral nervous system Edit
This differentiates the CNS from the PNS, which consists of neurons, axons, and Schwann cells. Oligodendrocytes and Schwann cells have similar functions in the CNS and PNS, respectively. Both act to add myelin sheaths to the axons, which acts as a form of insulation allowing for better and faster proliferation of electrical signals along the nerves. Axons in the CNS are often very short, barely a few millimeters, and do not need the same degree of isolation as peripheral nerves. Some peripheral nerves can be over 1 meter in length, such as the nerves to the big toe. To ensure signals move at sufficient speed, myelination is needed.
The way in which the Schwann cells and oligodendrocytes myelinate nerves differ. A Schwann cell usually myelinates a single axon, completely surrounding it. Sometimes, they may myelinate many axons, especially when in areas of short axons.  Oligodendrocytes usually myelinate several axons. They do this by sending out thin projections of their cell membrane, which envelop and enclose the axon.
During early development of the vertebrate embryo, a longitudinal groove on the neural plate gradually deepens and the ridges on either side of the groove (the neural folds) become elevated, and ultimately meet, transforming the groove into a closed tube called the neural tube.  The formation of the neural tube is called neurulation. At this stage, the walls of the neural tube contain proliferating neural stem cells in a region called the ventricular zone. The neural stem cells, principally radial glial cells, multiply and generate neurons through the process of neurogenesis, forming the rudiment of the CNS. 
The neural tube gives rise to both brain and spinal cord. The anterior (or 'rostral') portion of the neural tube initially differentiates into three brain vesicles (pockets): the prosencephalon at the front, the mesencephalon, and, between the mesencephalon and the spinal cord, the rhombencephalon. (By six weeks in the human embryo) the prosencephalon then divides further into the telencephalon and diencephalon and the rhombencephalon divides into the metencephalon and myelencephalon. The spinal cord is derived from the posterior or 'caudal' portion of the neural tube.
As a vertebrate grows, these vesicles differentiate further still. The telencephalon differentiates into, among other things, the striatum, the hippocampus and the neocortex, and its cavity becomes the first and second ventricles. Diencephalon elaborations include the subthalamus, hypothalamus, thalamus and epithalamus, and its cavity forms the third ventricle. The tectum, pretectum, cerebral peduncle and other structures develop out of the mesencephalon, and its cavity grows into the mesencephalic duct (cerebral aqueduct). The metencephalon becomes, among other things, the pons and the cerebellum, the myelencephalon forms the medulla oblongata, and their cavities develop into the fourth ventricle. 
Diagram depicting the main subdivisions of the embryonic vertebrate brain, later forming forebrain, midbrain and hindbrain.
AVERAGE BRAIN WEIGHTS OF DIFFERENT SPECIES
Sperm whale: 17 pounds (7.8 kilograms)
Elephant: 13.2 pounds (6 kilograms)
Bottle-nosed dolphin: 3.3 pounds (1.5 kilograms)
Human (adult): 3 pounds (1.36 kilograms)
Camel: 1.5 pounds (0.76 kilogram)
Hippopotamus: 1.3 pounds (0.58 kilogram)
Polar bear: 1.1 pounds (0.5 kilogram)
Chimpanzee: 14.7 ounces (420 grams)
Lion: 8.4 ounces (240 grams)
Dog: 2.5 ounces (72 grams)
Cat: 1.1 ounces (30 grams)
Rabbit: 0.4 ounce (11.5 grams)
Squirrel: 0.26 ounce (7.6 grams)
Hamster: 0.05 ounce (1.4 grams)
Bull frog: 0.008 ounce (0.24 gram)
Scientists have further divided each cerebral hemisphere into lobes named after the overlying bones of the skull: frontal (forehead area), temporal (on the sides above the ears), parietal (top part of the head), and occipital (back of the head) lobes.
The cerebral cortex is the portion of the brain that provides the most important distinctions between humans and other animals. It is responsible for the vast majority of functions that define what is meant by "being human." It enables humans not only to receive and interpret all kinds of sensory information, such as color, odor, taste, and sound, but also to remember, analyze, interpret, make decisions, and perform a host of other "higher" brain functions.
By studying animals and humans who have suffered damage to the cerebral cortex, scientists have found that the various lobes house areas with specific functions. The frontal lobes contain motor areas that generate impulses for voluntary movements. An area usually located in the left frontal lobe is called Broca's area. It coordinates the movements of the mouth involved in speaking. The parietal lobes contain general sensory areas that receive impulses from receptors in the skin. The temporal lobes contain auditory areas (receive impulses from the ears for hearing) and olfactory areas (receive impulses from receptors in the nose for smell). The occipital lobes contain visual areas that receive impulses from the retinas of the eyes. Different areas in the occipital lobes are concerned with judging distance and other spatial relationships.
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Those parts of the brain involved in the reception and interpretation of sensory stimuli are referred to collectively as the sensorium. The cerebral cortex has several regions that are necessary for sensory perception. From the primary cortical areas of the somatosensory, visual, auditory, and gustatory senses to the association areas that process information in these modalities, the cerebral cortex is the seat of conscious sensory perception. In contrast, sensory information can also be processed by deeper brain regions, which we may vaguely describe as subconscious—for instance, we are not constantly aware of the proprioceptive information that the cerebellum uses to maintain balance. Several of the subtests can reveal activity associated with these sensory modalities, such as being able to hear a question or see a picture. Two subtests assess specific functions of these cortical areas.
The first is praxis, a practical exercise in which the patient performs a task completely on the basis of verbal description without any demonstration from the examiner. For example, the patient can be told to take their left hand and place it palm down on their left thigh, then flip it over so the palm is facing up, and then repeat this four times. The examiner describes the activity without any movements on their part to suggest how the movements are to be performed. The patient needs to understand the instructions, transform them into movements, and use sensory feedback, both visual and proprioceptive, to perform the movements correctly.
The second subtest for sensory perception is gnosis, which involves two tasks. The first task, known as stereognosis, involves the naming of objects strictly on the basis of the somatosensory information that comes from manipulating them. The patient keeps their eyes closed and is given a common object, such as a coin, that they have to identify. The patient should be able to indicate the particular type of coin, such as a dime versus a penny, or a nickel versus a quarter, on the basis of the sensory cues involved. For example, the size, thickness, or weight of the coin may be an indication, or to differentiate the pairs of coins suggested here, the smooth or corrugated edge of the coin will correspond to the particular denomination. The second task, graphesthesia, is to recognize numbers or letters written on the palm of the hand with a dull pointer, such as a pen cap.
Praxis and gnosis are related to the conscious perception and cortical processing of sensory information. Being able to transform verbal commands into a sequence of motor responses, or to manipulate and recognize a common object and associate it with a name for that object. Both subtests have language components because language function is integral to these functions. The relationship between the words that describe actions, or the nouns that represent objects, and the cerebral location of these concepts is suggested to be localized to particular cortical areas. Certain aphasias can be characterized by a deficit of verbs or nouns, known as V impairment or N impairment, or may be classified as V–N dissociation. Patients have difficulty using one type of word over the other. To describe what is happening in a photograph as part of the expressive language subtest, a patient will use active- or image-based language. The lack of one or the other of these components of language can relate to the ability to use verbs or nouns. Damage to the region at which the frontal and temporal lobes meet, including the region known as the insula, is associated with V impairment damage to the middle and inferior temporal lobe is associated with N impairment.
Interactive Link Questions
Watch this video that provides a demonstration of the neurological exam&mdasha series of tests that can be performed rapidly when a patient is initially brought into an emergency department. The exam can be repeated on a regular basis to keep a record of how and if neurological function changes over time. In what order were the sections of the neurological exam tested in this video, and which section seemed to be left out?
Watch this video for an introduction to the neurological exam. Studying the neurological exam can give insight into how structure and function in the nervous system are interdependent. This is a tool both in the clinic and in the classroom, but for different reasons. In the clinic, this is a powerful but simple tool to assess a patient&rsquos neurological function. In the classroom, it is a different way to think about the nervous system. Though medical technology provides noninvasive imaging and real-time functional data, the presenter says these cannot replace the history at the core of the medical examination. What does history mean in the context of medical practice?
Read this article to learn about a young man who texts his fiancée in a panic as he finds that he is having trouble remembering things. At the hospital, a neurologist administers the mental status exam, which is mostly normal except for the three-word recall test. The young man could not recall them even 30 seconds after hearing them and repeating them back to the doctor. An undiscovered mass in the mediastinum region was found to be Hodgkin&rsquos lymphoma, a type of cancer that affects the immune system and likely caused antibodies to attack the nervous system. The patient eventually regained his ability to remember, though the events in the hospital were always elusive. Considering that the effects on memory were temporary, but resulted in the loss of the specific events of the hospital stay, what regions of the brain were likely to have been affected by the antibodies and what type of memory does that represent?
Watch the video titled &ldquoThe Man With Two Brains&rdquo to see the neuroscientist Michael Gazzaniga introduce a patient he has worked with for years who has had his corpus callosum cut, separating his two cerebral hemispheres. A few tests are run to demonstrate how this manifests in tests of cerebral function. Unlike normal people, this patient can perform two independent tasks at the same time because the lines of communication between the right and left sides of his brain have been removed. Whereas a person with an intact corpus callosum cannot overcome the dominance of one hemisphere over the other, this patient can. If the left cerebral hemisphere is dominant in the majority of people, why would right-handedness be most common?
Watch this short video to see an examination of the facial nerve using some simple tests. The facial nerve controls the muscles of facial expression. Severe deficits will be obvious in watching someone use those muscles for normal control. One side of the face might not move like the other side. But directed tests, especially for contraction against resistance, require a formal testing of the muscles. The muscles of the upper and lower face need to be tested. The strength test in this video involves the patient squeezing her eyes shut and the examiner trying to pry her eyes open. Why does the examiner ask her to try a second time?
Watch this video to see a quick demonstration of two-point discrimination. Touching a specialized caliper to the surface of the skin will measure the distance between two points that are perceived as distinct stimuli versus a single stimulus. The patient keeps their eyes closed while the examiner switches between using both points of the caliper or just one. The patient then must indicate whether one or two stimuli are in contact with the skin. Why is the distance between the caliper points closer on the fingertips as opposed to the palm of the hand? And what do you think the distance would be on the arm, or the shoulder?
Watch this video to see how to test reflexes in the abdomen. Testing reflexes of the trunk is not commonly performed in the neurological exam, but if findings suggest a problem with the thoracic segments of the spinal cord, a series of superficial reflexes of the abdomen can localize function to those segments. If contraction is not observed when the skin lateral to the umbilicus (belly button) is stimulated, what level of the spinal cord may be damaged?
Watch this short video to see a test for station. Station refers to the position a person adopts when they are standing still. The examiner would look for issues with balance, which coordinates proprioceptive, vestibular, and visual information in the cerebellum. To test the ability of a subject to maintain balance, asking them to stand or hop on one foot can be more demanding. The examiner may also push the subject to see if they can maintain balance. An abnormal finding in the test of station is if the feet are placed far apart. Why would a wide stance suggest problems with cerebellar function?
The Peripheral Nervous System (PNS)
The peripheral nervous system connects the central nervous system to environmental stimuli to gather sensory input and create motor output.
Discuss the organization of the peripheral nervous system
- The peripheral nervous system (PNS) provides the connection between internal or external stimuli and the central nervous system to allow the body to respond to its environment.
- The PNS is made up of different kinds of neurons, or nerve cells, which communicate with each other through electric signaling and neurotransmitters.
- The PNS can be broken down into two systems: the autonomic nervous system, which regulates involuntary actions such as breathing and digestion, and the somatic nervous system, which governs voluntary action and body reflexes.
- The autonomic nervous system has two complementary parts: the sympathetic nervous system, which activates the “fight-or-flight-or-freeze” stress response, and the parasympathetic nervous system, which reacts with the “rest-and-digest” response after stress.
- The somatic nervous system coordinates voluntary physical action. It is also responsible for our reflexes, which do not require brain input.
- afferent: Leading toward the central nervous system.
- efferent: Leading away from the central nervous system.
- polysynaptic reflex: Involves at least one interneuron between the sensory and motor neurons.
- monosynaptic reflex: Involves a single synapse between the sensory neuron that receives the information and the motor neuron that responds.
- somatic nervous system: The part of the peripheral nervous system that transmits signals from the central nervous system to skeletal muscle and from receptors of external stimuli to the central nervous system, thereby mediating sight, hearing, and touch.
- autonomic nervous system: The part of the nervous system that regulates the involuntary activity of the heart, intestines, and glands, including digestion, respiration, perspiration, metabolism, and blood-pressure modulation.
- sympathetic nervous system: The part of the autonomic nervous system that raises blood pressure and heart rate, constricts blood vessels, and dilates the pupils in situations of stress.
- parasympathetic nervous system: One of the divisions of the autonomic nervous system located between the brain and the spinal cord slows the heart and relaxes the muscles.
The peripheral nervous system (PNS) is one of the two major components of the body’s nervous system. In conjunction with the central nervous system (CNS), the PNS coordinates action and responses by sending signals from one part of the body to another. The CNS includes the brain, brain stem, and spinal cord, while the PNS includes all other sensory neurons, clusters of neurons called ganglia, and connector neurons that attach to the CNS and other neurons.
The nervous system: The human nervous system, including both the central nervous system (in red: brain, brain stem, and spinal cord) and the peripheral nervous system (in blue: all other neurons and receptors).
Divisions of the Peripheral Nervous System
The PNS can also be divided into two separate systems: the autonomic nervous system and the somatic nervous system.
Autonomic Nervous System
The autonomic nervous system regulates involuntary and unconscious actions, such as internal-organ function, breathing, digestion, and heartbeat. This system consists of two complementary parts: the sympathetic and parasympathetic systems. Both divisions work without conscious effort and have similar nerve pathways, but they generally have opposite effects on target tissues.
The sympathetic nervous system activates the “fight or flight” response under sudden or stressful circumstances, such as taking an exam or seeing a bear. It increases physical arousal levels, raising the heart and breathing rates and dilating the pupils, as it prepares the body to run or confront danger. These are not the only two options “fight or flight” is perhaps better phrased as “fight or flight or freeze,” where in the third option the body stiffens and action cannot be taken. This is an autonomic response that occurs in animals and humans it is a survival mechanism thought to be related to playing dead when attacked by a predator. Post-traumatic stress disorder (PTSD) can result when a human experiences this “fight or flight or freeze” mode with great intensity or for large amounts of time.
The parasympathetic nervous system activates a “rest and digest” or “feed and breed” response after these stressful events, which conserves energy and replenishes the system. It reduces bodily arousal, slowing the heartbeat and breathing rate. Together, these two systems maintain homeostasis within the body: one priming the body for action, and the other repairing the body afterward.
Somatic Nervous System
The somatic nervous system keeps the body adept and coordinated, both through reflexes and voluntary action. The somatic nervous system controls systems in areas as diverse as the skin, bones, joints, and skeletal muscles. Afferent fibers, or nerves that receive information from external stimuli, carry sensory information through pathways that connect the skin and skeletal muscles to the CNS for processing. The information is then sent back via efferent nerves, or nerves that carry instructions from the CNS, back through the somatic system. These instructions go to neuromuscular junctions—the interfaces between neurons and muscles—for motor output.
The somatic system also provides us with reflexes, which are automatic and do not require input or integration from the brain to perform. Reflexes can be categorized as either monosynaptic or polysynaptic based on the reflex arc used to perform the function. Monosynaptic reflex arcs, such as the knee-jerk reflex, have only a single synapse between the sensory neuron that receives the information and the motor neuron that responds. Polysynaptic reflex arcs, by contrast, have at least one interneuron between the sensory neuron and the motor neuron. An example of a polysynaptic reflex arc is seen when a person steps on a tack—in response, their body must pull that foot up while simultaneously transferring balance to the other leg.