A simple reflex with only a single synapse between the sensory and motor neurons is known as a

The Inflammatory Reflex Arc

A neural reflex arc is characterized by peripheral afferent sensory input that is transmitted to the central nervous system and processed; the resultant action is carried by efferent motor neurons to the periphery. Thus, at least two synaptic connections are involved in every reflex arc. The vagus nerve mediates multiple reflex arcs across the cardiovascular, gastrointestinal, and endocrine systems. As the primary parasympathetic nerve, it is no surprise that it also plays a role in mediating the immune response. It is composed of 80% sensory fibers. Afferent sensory vagus neurons transmit peripheral signals to brainstem nuclei; efferent motor vagus neurons project to the periphery and signal primarily viaacetylcholinesterase both at pre- and postganglionic neurons. Vagal neural arcs are integrated in the brain within the dorsal vagal complex, which is comprised of the nucleus tractus solitarius, dorsal motor nucleus of the vagus, and the area postrema.26 In addition to vagally mediated reflex arcs, the inflammatory signals carried via the afferent vagal fibers also play a role in mediating the fever response and regulating the HPA axis and subsequent glucocorticoid secretion.27

The reflex arc

The reflex arc is made up of an afferent pathway from a receptor and an efferent pathway to an effector: it is similar in outline to a negative feedback control system (Fig. 13.3). Indeed the whole range of regulatory reflexes are themselves negative feedback control systems. However, the pathway outlined in the diagram is appropriate not only for regulatory reflexes but also for two other types of reflex: the nociceptive reflex in which a painful or harmful stimulus causes the organism to withdraw itself or attempt to remove the stimulus, and the other type of reflex in which the organism produces a change of position or state in order to ensure its survival. The simplest entirely neuronal reflex arc consists of two neurones only. Although a single neurone reflex may appear to be impossible, the branching of a sensory nerve fibre can permit a sensory impulse travelling towards the spinal cord to pass antidromically down another branch and produce a response at a normally sensory termination. Such an axon reflex is observed in the control of the skin circulation (see p. 235). Leaving this anomalous example aside, however, it is even debatable whether a true two-neurone reflex can exist. The stretch reflex - contraction of a muscle in response to being stretched - is described as a two-neurone reflex, but if all the concurrent actions which permit that muscle to contract are included, many more neurones are involved.

However, what is normally described as the simplest reflex takes the following form (Fig. 13.4). The reflex pathway will be described in terms of a spinal sensory nerve, the spinal pathways and spinal motor nerves; reflexes involving cranial sensory and motor nerves follow analogous routes. In many homeostatic reflexes the effector pathway is hormonal. A sensory nerve enters the spinal cord by a dorsal root or its cranial equivalent. The cell body of the spinal sensory afferent is in the dorsal root ganglion (the cranial equivalent is the nucleus of the cranial nerve). This is the afferent limb of the reflex arc. The neurone then synapses with an anterior horn cell - the cell body of a motor nerve - and the motor axon then leaves the cord in the ventral root of the spinal nerve, as the efferent limb of the reflex arc. Such a simple reflex - and probably only the stretch reflex is as simple as this - is usually accompanied by synergistic reflexes or other additional reactions. A muscle cannot easily shorten unless its antagonist muscle relaxes; contraction of an extensor muscle usually requires relaxation of a flexor muscle, or vice versa. This is achieved by stimulation of other interneurones (internuncial or messenger neurones) which inhibit the motor nerve to the opposing muscle. The axons of such internuncial neurones may stay in one segment of the spinal cord or project up or down to other segments to activate additional pathways.

Because most reflexes occur at spinal level and are modified or inhibited by impulses from higher in the spinal cord or from the brain itself, damage to the spinal cord above the level of the reflex pathway or damage to the brain may leave a spinal reflex intact or even uncover a fundamental response normally masked by control from the higher levels. Normal reflex activity may persist during general anaesthesia but be abolished by local anaesthetics which block the sensory pathways. The complex responses which prevent the biting of the lips or cheeks during mastication may fail to operate when the mandibular nerve is blocked after carrying out treatment in the lower dental arch.

Assessing the Sacral Reflex Arc

The “bulbocavernosus” reflex (penile-cavernosus reflex) assesses the afferent and efferent pathways consisting of the pudendal nerve, sacral roots, and sacral spinal cord (S2, S3, and S4 segments). The dorsal nerve of the penis (or clitoris) is electrically stimulated and recordings are made from the bulbocavernosus muscle or external anal sphincter, usually with a concentric needle (Fig. 45.8). Testing may therefore be of value in the assessment of the sacral roots in patients with bladder dysfunction suspected to be secondary to cauda equina damage or damage to the lower motor neuron pathway.

Baroreflex and Cardiovascular Autonomic Function

Autonomic reflex arcs are complex in nature due to the recruitment of rapid and synchronized sympathetic and parasympathetic activation across central and peripheral neuronal pathways. For example, behavior-dependent increases in blood pressure are enabled and moderated by the baroreflex (Janig and Habler, 2003) and failure of this autonomic reflex arc causes loss of consciousness due to cerebral hypoperfusion. During the first 10–15 s of standing (orthostasis), venous pooling occurs as gravity attracts around 750 mL of blood flow to the leg, pelvic and abdominal capacitance veins. To counteract venous pooling in order to maintain cerebral perfusion, cardiopulmonary mechanoreceptors and arterial baroreceptors in the aortic arch and carotid sinus detect changes in vascular contraction and send afferent signals to the brainstem to upregulate peripheral sympathetic activity to increase peripheral vascular resistance, venous tone and heart rate to adequately perfuse neural tissue (Smit et al., 1999).

Cerebral perfusion is dependent on sympathetic, parasympathetic and sensory innervation of the cerebral vasculature; however, the complexity of neurovascular coupling allows for the breakdown of cerebral perfusion, which manifests most profoundly as syncope (fainting). Intracranial pressure and local arterial pressure maintain cerebral perfusion pressure (the difference between intracranial pressure and mean arterial pressure) at approximately 80 mmHg and excessive fluctuations are prevented by autoregulation of cerebral blood flow (CBF), regardless of peripheral variations in blood pressure (Van Lieshout et al., 2003). However, cerebral perfusion pressure is dependent on system arterial pressure, which is itself dependent on cardiac output and peripheral vascular resistance. Therefore, a reduction in either of these peripheral factors can cause reductions in cerebral perfusion pressure. Should cerebral perfusion pressure drop below approximately 70 mmHg, the brain becomes inadequately perfused with oxygen and metabolites, predisposing to loss of consciousness (Rosner et al., 1995).

Middle Ear Muscle Reflex Pathways

The middle ear muscle reflex is another major feedback system to the auditory periphery. The pathways for the stapedius reflex to one side (ipsilateral side) are shown inFig. 128.14. The stapedius and tensor tympani muscles are the target organs of the middle ear muscle reflex and are innervated by the efferent fibers that originate in the motoneurons around and near the facial and trigeminal nerve nuclei, respectively. Activation of this neural pathway results in contraction of the middle ear muscles in response to specific sound stimuli. Contraction of the stapedius and tensor tympani muscles exerts forces perpendicular to the stapes and malleus, respectively, to increase the impedance of the ossicular chain.86 The detailed pathway of the stapedial reflex arc is shown inFig. 128.14. Acoustic stimuli presented to either ear activate stapedius muscle contraction in both ears, similar to the consensual pupillary response to light. The reflex therefore begins as afferent auditory input from the cochleae, and the signal is transmitted along the auditory nerve to the cochlear nuclei. Interneurons that have not yet been identified but may be located in the ventral cochlear nucleus,87 projecting either directly or indirectly from the cochlear nuclei to the stapedius motoneurons (seeFig. 128.14), although these central pathways are not completely understood at this point. Stapedius motoneurons project to the middle ear by way of the facial nerve to innervate the stapedius muscle (stapedial nerve), which is attached to the posterior neck of the stapes capitulum; contraction stiffens the stapes superstructure and increases middle ear impedance.

Acoustic impedance measurements have proven that the stapedius is the primary sound-evoked middle ear muscle.88–90 Unlike the case in some animal models, in which both the stapedius and tensor tympani contract in response to sound, the stapedius reflex is the dominant sound-evoked pathway in humans.90,91 Two major functions of the stapedius reflexes have been proposed: (1) modulation of middle ear impedance and attenuation of acoustic energy that reaches the cochlea92–94 and (2) high-pass filtration of low-frequency sound (background noise) to prevent masking of speech frequencies. The function of the middle ear muscle reflex pathway appears to be protective; contraction of the middle ear muscles results in frequency-dependent sound attenuation in the presence of intense acoustic stimuli, an effect that is more pronounced for lower sound frequencies.95,96 This frequency-specific attenuation of the middle ear muscle reflex supports the hypothesis that this reflex pathway preserves speech frequency information from being masked by intense background noise, which is typically lower in frequency.97–101 The stapedius muscle also contracts in response to internally or self-generated vocalization;99 thus it may help prevent self-stimulation.

1 VOR

The reflex arc for the VOR is a three-neuron pathway connecting the primary vestibular afferents arising from the semicircular canals, to the VOR relay neurons in vestibular nuclei, and finally to motoneurons innervating the extraocular muscles. VOR relay neurons are either excitatory or inhibitory in their synaptic action, and induce either contraction or relaxation of the extraocular muscles via excitation or inhibition of motoneurons. There are a number of parallel pathways connecting the three semicircular canals (horizontal, anterior, and posterior) and the two otolith organs (saccule and utricle) in each labyrinth to the six extraocular muscles in each eye (medial and lateral rectus, superior and inferior rectus, superior and inferior oblique). These pathways operate in concert under conditions of free head movement, but in an experimental setup they are stimulated separately by giving yaw, pitch, roll or linear acceleration.

The horizontal VOR is tested by sinusoidal or velocity-step head rotation on the horizontal plane, and the VOR gain is measured as the ratio of the attained eye velocity to the applied head velocity. Sinusoidal rotation is convenient for measuring the gain and phase of the VOR separately, while velocity steps enable us to separate the VOR responses, which arise with different latencies, into their constituent components. Measurement of the VOR is performed in the dark or with the eyes closed while the whole body is rotating.

Human Stretch Reflexes

The stretch reflex arc may be tested in human subjects by the application of fast stretch or vibration to the primary ending of the muscle spindle to produce a tendon jerk, or by the electrical stimulation of Ia afferent fibers in the appropriate peripheral nerve to evoke an H reflex. Intraneural recordings have demonstrated that the afferent volley of the tendon jerk and H reflex are dissimilar in the types of afferents activated, the pattern of activity in each afferent, the sources of the afferent activity, and their degree of dispersion (Burke, Gandevia, and McKeon 1983). There are good reasons for believing that neither reflex is exclusively monosynaptic.

Sustained activity of the stretch reflex arc (the tonic stretch reflex) normally is seen only when excitability is increased by mental or physical activation (reinforcement) or when a vibrator is applied to muscle belly or tendon (the tonic vibration reflex, TVR). Although vibration initiates a tonic reflex contraction, it diminishes tendon jerks or H reflexes simultaneously (Lance, de Gail, and Neilson 1966) by the process of presynaptic inhibition (Gillies et al. 1969).

In patients with upper motor neuron lesions, lower motor neuron excitability is increased so that tonic stretch reflexes and tendon jerks are thereby increased. Muscles distant from a point of percussion may respond reflexly to afferent impulses evoked by the transmission of a vibration wave from the place of impact (Lance and de Gail 1965). This phenomenon, known as irradiation of reflexes, is accounted for by the increased sensitivity of stretch reflexes so that the propagated vibration wave initiates a reflex contraction from each of the muscle bellies traversed, much as though the tendon of each muscle had been tapped in succession (Fig. 1.7). When a spastic upper limb is percussed, all muscle groups in that limb may contract by means of excitation of their own reflex arcs. Flexion of the fingers and thumb often is seen under these circumstances. Flexion of the thumb in response to flipping the terminal phalanx of the index finger has been given a particular mystique as “Hoffmann's sign,” but the same thumb response may be seen on percussion of the flexed fingers, the radius, or indeed the shoulder joint, in any patient with hyperreflexia. It is thus a nonspecific index of motor neuron excitability elicited by a vibration wave passing through the long flexors of the thumb.

In spasticity, if a muscle suddenly is stretched and the stretch is sustained, the stretch reflex arc will be activated repetitively at 5 to 8 Hz (clonus).

Spinal Cord Lesions

The spinobulbar reflex arc is crucial in the control of bladder function in health. Following spinal cord lesions, interruption of this reflex, along with loss of supraspinal control, results in a local spinal reflex that drives bladder contractions. The localization of lesions can be guided by the type of bladder dysfunction observed.

The hyperreflexic neurogenic (spastic) bladder occurs following lesions that interrupt the connections between the pontine micturition center and sacral cord micturition centers. Commonly these myelopathic conditions cause quadriplegia or paraplegia. Clinically, patients present with detrusor contraction during bladder filling leading to detrusor overactivity, characterized by urinary frequency, urgency, urge incontinence, and inability to initiate micturition voluntarily. Bladder capacity is reduced, although residual urine may be increased. On examination, the bulbocavernosus and anal reflexes are preserved.

Autonomous neurogenic bladder (detrusor areflexia) may occur with complete lesions below the T12 segment that involve the conus medullaris and cauda equina. Common pathologies include sacral myelomeningoceles and tumors of the conus medullaris and cauda equina. This type of neurogenic bladder also occurs during the initial shock phase following spinal cord injury; gradually over the course of weeks new reflexes emerge to drive bladder emptying and cause detrusor contractions in response to low filling volumes. Clinically there is urinary retention since the tone of the detrusor muscle is abolished and there is no awareness of fullness. Overflow incontinence and increased residual urine develop later. On examination, associated saddle anesthesia with absence of the bulbocavernosus and superficial anal reflexes are common. Anal sphincter control is often affected similarly.

Motor paralytic bladder results from lesions involving the efferent motor fibers to the detrusor or the detrusor motor neurons in the sacral spinal cord. Common pathologies include lumbar spinal stenosis, lumbosacral meningomyelocele, or following abdominoperineal resection or radical hysterectomy. Clinically painful urinary retention or impaired bladder emptying is the presenting feature, and residual urine is markedly increased. The bulbocavernosus and superficial anal reflexes are usually absent, but sacral and bladder sensation are preserved.

Sensory paralytic bladder is caused by impairment of the afferent pathways innervating the bladder or by dysfunction of the posterior columns or lateral spinothalamic tract in the spinal cord. Classically, this condition has been described in tabes dorsalis, syringomyelia, and diabetes mellitus. Voluntary initiation of micturition may be retained. On examination, the bulbocavernosus and superficial anal reflexes are variably absent, decreased, or present.

This classification system does not often reflect clinical practice and deviations from these descriptions often exist. Spinal shock is quite variable in presentation, and the neurophysiology of recovery from spinal shock has been characterized mainly in cats where, following injury, C fibers emerge as the major afferents, forming a spinal segmental reflex that results in automatic voiding. The abnormally overactive, small-capacity bladder that characterizes spinal cord disease causes patients to experience urinary urgency and frequency; however, patients with complete transection of the cord may not complain of urgency. If detrusor overactivity is severe, incontinence is highly likely.

PUPILLARY RESPONSES TO LIGHT

The parasympathetic reflex arc begins in the retina, traverses the base of the brain, runs through the midbrain, and returns to the pupil (see Chapters 8 and 9Chapter 8Chapter 9). Disorders altering pupillary constriction typically affect the midbrain or cranial nerve III. Compression of the superior colliculus (e.g., by a pineal region mass) interferes with input to the pretectal nuclei, resulting in pupils that are large (because the sympathetic system is not affected), unreactive to light, and sometimes displaying hippus. Lesions affecting the area of the Edinger‐Westphal nucleus and the origins of cranial nerve III are the most important because this area is adjacent to the superior pole of the midbrain reticular formation. Because the descending sympathetic efferent fibers also traverse this portion of the brain stem, dysfunction produces pupils that are midposition (4 to 6 mm in diameter), unreactive to light, and frequently slightly irregular. Such pupils are an ominous finding, usually indicating that coma is due to structural damage affecting the upper midbrain, and unless its etiology can be reversed quickly, the patient's coma is usually irreversible. Because the pupillary constrictor has a muscarinic, rather than a nicotinic, acetylcholine receptor, it is not affected by drugs given to block neuromuscular transmission. However, it is affected by systemic antimuscarinic drugs (e.g., atropine), so one must be cautious about interpreting the examination if such agents are being used.

Unilateral loss of pupillary constriction in the comatose patient may rarely indicate subarachnoid hemorrhage from an internal carotid aneurysm that compresses cranial nerve III at the origin of the posterior communicating artery (Video 32, Cranial Nerve III Palsy). Much more commonly, such a finding indicates the presence of a mass lesion that has shifted the diencephalon laterally. Although older studies suggested that this finding arose from compression of the third cranial nerve by the herniating temporal lobe, the unilaterally dilated pupil appears to develop before actual movement of the medial temporal structures over the tentorial edge. Ropper's work demonstrates that unilateral pupillary dilation results from traction on cranial nerve III produced when the diencephalon, being pushed away from an expanding lateral mass, pulls the midbrain with it. Because cranial nerve III is tethered anteriorly at the cavernous sinus, the nerve ipsilateral to the mass is subjected to stretching and the pupil dilates. Early in the course of this process, therapies that decrease the degree of shift (e.g., administration of mannitol) can reverse the pupillary dilation.

The sympathetic pathways begin in the hypothalamus, descend through the brain stem and spinal cord to the first thoracic level, and then exit the central nervous system to traverse the face and reach the pupil. Most sedative drugs produce bilateral small pupils by antagonizing sympathetic outflow at the hypothalamic level; other agents, such as opiates, appear to have an additional effect of stimulating the parasympathetic system, resulting in very small (pinpoint) pupils. Lesions affecting the sympathetic system below the midbrain do not directly affect consciousness.

ANATOMY OP THE CARDIOVASCULAR REFLEX ARC

Elements of the cardiovascular reflex arc are summarized in Fig. 1. and Table 1. They have been detailed earlier (Refs 28,30). The peripheral pathway of the reflex arc originates in the stretch receptors (carotid sinus, aortic arc, cardiac wall). The perikaryon is a pseudounipolar cell in the superior or inferior ganglia having a central process to terminate in the medulla oblongata, in the nucleus of the solitary tract (NST). This is the first or afferent neuron of the reflex arc.

TABLE 1. Components of the Baroreceptor Reflex Arc

Perikarya in the area of the NST seem to be the second or central neurons having more different projection possibilities. There is a simple or short reflex directly to the efferent neurons (2a in Fig. 1 and Table 1) connecting the NST with the periphery without involving higher centers in the reflex mechanisms. Such short loop reflexes are generally believed to belong to the vegetative nervous system. Ascending axons from the NST to higher cardiovascular modulatory centers represent the other type of the baroreceptor output (2b in Fig. 1. and Table 1). Our knowledge concerning their topography, termination and chemical character is going to be summarized later on. Axons from higher cardiovascular modulatory centers descend to terminate on the efferent neurons (2c in Fig. 1 and Table 1). Accordingly, the origin and the termination of the long loop and the short loop is the same, but higher modulatory centers are inserted between the afferent and efferent pathways in the former establishing the anatomical basis of a wide range modulation in the cardiovascular mechanisms. Consequently, neuronal structures involved in the cardiovascular regulation (hypothalamus, limbic system, midbrain-pontine cellgroups) receive the neural cardiovascular information only through the NST so exerting their effects indirectly, over the efferent neurons.

The efferent neurons form the third component of the cardiovascular reflex arc. These cells are located in the medulla oblongata and the spinal cord and their axons leave in the vagal nerve or in the spinal sympathetic nerve to reach the periphery (3a in Fig. 1 and Table 1). They are presynaptic neurons as before reaching the periphery have a with-over in the vegetative ganglia (vagal, sympathic, cardiac). Hence this last part of the reflex arc consists of post-ganglionary fibers (3b in Fig. 1 and Table 1).