Chapter 02: Spontaneous Pupillary Changes in Darkness

CHAPTER 2 Spontaneous Pupillary Changes in Darkness CONTENTS A. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . 76 B. Fluctuations of Autonomic Equilibrium . . . . . 76 C. Pupillary Movements versus Respiration and Pulse Rate . . . . . . . . . . . . . . . . . . . . . . . . . 77 A. Summary The effectiveness of various lights and of other stimuli upon the pupil cannot be judged without some idea of how the pupils behave spontaneously in darkness, for it is on the background of spontaneous fluctuations of tone and activity of the system that these reactions are superimposed. Lack of this consideration has given rise to much complicated argument in the past. This short chapter thus forms a preamble for the following chapters on the physiology of the light reflex (Chapter 3), on pupillary reactions to dark stimuli (Chapter 4), on the effects of near-vision efforts (Chapter 5), and on those elicited by psychosensory stimula- tion (Chapter 6). All these reactions are modified in amplitude and time course by shifts in autonomic nervous equilibrium, brought on chiefly by changing levels of arousal, as described in more detail in Chapter 10. In addition, the relations between breathing and cardiovascular activity on one side and pupillary size and reflexes on the other are analyzed. In healthy, alert individuals these functions are not related in timing. When, under certain unusual or pathologic circumstances they coincide, they are triggered together by central nervous mechanisms (see further in Chapter 46). B. Fluctuations of Autonomic Equilibrium Until Cohn's and Du Bois-Reymond's magnesium flash photographs in 1888 no one had ever seen the pupils in darkness; and it certainly was surprising to discover how large they could become in normal people, once the light needed for observation was removed. 1 Another fifty years elapsed until high-speed, infraredsensitive film made possible cinematography of iris movements in virtual darkness, and an additional 20 years before such observations could be done easily and quickly with the help of infrared-sensitive electronic devices. Pupillary behavior in darkness could then be studied over longer periods. The pupils of healthy, well-rested subjects in darkness usually are quite stable for minutes at a time. The normal "pupillary unrest" that is so impressive when the subject's eyes are watched in diffuse light ceases promptly as soon as the light is turned off. The pupils remain large and steady as long as the subject stays fully alert; but sooner or later, under the influence of boredom, fatigue takes over and the pupils begin to oscillate. Such "fatigue waves" and a steadily declining pupil size almost always wilJ be encountered eventualJy when subjects remain quietly in darkness for lengthy periods without anything to do. This was sometimes forgotten, and the pupillary changes that occurred with time were thought to be caused 1. Even today clinicians are so accustomed to examining the pupils in light that the "normal" pupillary size generally is grossly underestimated. 76 by the experimental procedure or by the drug used. It should thus be stressed that fatigue waves can be very large indeed, resulting in shifts of pupil size of several millimeters, and in profound alterations of responses to standard light or other stimuli. In animals these spontaneous changes are even more marked than they are in man. Fatigue waves differ in timing and extent from pupillary unrest induced by steady light. Characteristically, fatigue waves are rather slow (3 seconds or longer) and vary in depth from a just perceptible wavering to huge ups and downs that cover a great part of the range of pupillary mobility, as just mentioned, while lightinduced "unrest" consists of small wavelets that increase in frequency with the intensity of illumination. The constant modulation of pupillary responses brought about by these spontaneous shifts in autonomic innervation is one reason why results of pupillary experiments that are given only as averages, or as percent changes over a preceding condition, are of limited usefulness: without the original data concerning pupillary size and movements one never can be sure of what actually happened. In the past authors would present detailed individual case reports and experimental protocols, and only then would discuss the general trend and meaning. The original facts may be extremely useful even when the authors' conclusions are erroneous. Because of the huge volume of published work today, such extensive renditions are no longer possible. But often the original data 2. Spontaneous Pupillary Changes in Darkness 77 / only minutes, with pupils that fluctuate wildly from one moment to the next. These differences are related partly to the subjects' general state of health and degree of tiredness at the time of the experiment. In addition, each individual has a characteristic pattern of responding to a given situation, repeated more or Jess regularly in every experiment (Figure 2-1). Since this pattern is the same in identical twins, it must be anchored in the genetic makeup of the individual. could be tabulated without much waste of space, while the boiled-down information alone leaves the reader with unanswered questions. Age also must be considered, since with advancing decades there is a steady loss of central inhibition and hence of pupil size in darkness (see Chapter 10). Further, there are wide differences between subjects: one will sit quietly for hours, hardly blinking an eye, with pupils large and steady as a rock; yet under the same circumstances, another will squirm and droop off after C. Pupillary Movements versus Respiration and Pulse Rate hemaglobinuria, asthma, and apical tuberculosis, to cite only one author (Somogyi, 1913). Other lists were no more inspiring. One group of authors said mydriasis was evoked only by forced inspiration, as it is by other forceful motor efforts (Vigoroux, 1863; Pieraccini, 1928; among many), or by sensations brought on by the act of deep breathing (Ingalls, 1923; and others). Both these possibilities indeed exist. Another suggestion was that blood which was pushed forcefully into the iris vessels by deep breaths or by the heartbeat caused pupillary changes by local vascular engorgement. Throughout the years the opinion has been widespread that the pupils are influenced by the pulse, the respiratory rhythm, or both. They were said to dilate during inspiration, to contract during expiration, and to follow the pulse with small oscillations. Statements that this "of course is well known" abound in the literature; and "respiratory hippus" is mentioned in current texts. In some of these reports, "inspiration mydriasis" was considered normal, in others pathologic. Among the latter, conditions held responsible included sciatica, constipation, typhus, anemia, SI• C1 8 7 e 5 ; 2 LIGHT UOHT +H+t+++-11111111111111 TIIIE t. e e ______ IN 111111 11111 II 0.1 SECONO UNITS-+ ....._ .......................................................................................... ..._..._....... min.➔ B 1 8 7 6 0 1 2 I 2 8 7 ,......,_ 6 9 2 \ 3 3 8 7 6 8 t e E 7 6 . ) 2 I 3 4 . 0 min. ➔ ~~ I ,,, ,. ,. 2 . 3 Figure 2-1. Spontaneous pupillary movements in darkness. A and B: Pupillary behavior of two healthy young men during 3½ minutes in darkness on four different days, at intervals of I week (lines I to 4). The records were taken between 5 and 6 P.M. Both subjects were conscientious dental students who had worked hard in the clinic all afternoon. The first subject (A) quickly became sleepy as he sat in the dark. The second (B ) did not. The records show pupillary diameter (in mm) plotted against time (in minutes). They were obtained by contracting the usual time axis of the pupillograms to one-twentieth of its usual length, by measuring the pupillary size at the beginning of each successive second of the original record, and plotting each measurement as a small square on the graph. Subject A's pupils became unsteady already within the first minute of the experiment. In contrast, subject B's pupils never showed more than the slightest variations. The longe t test run on B was 90 minutes, but even then his pupils did not waver. C 1 and C2: Light reflexes of the students, elicited by ten consecutive 1-second bright light flashes, with 2-minute rest periods interposed (white light, 5° retinal area, centrally fixated, 7.5 log units above the subjects' scotopic visual threshold). The individual reflexes were superimposed. Note the marked variability in reactions for A (C 1), and the tight bundle of curves for B (C'). 1111111 78 I I. Anatomy and Physiology It does not appear farfetched that basic biologic rhythms such as breathing and the pulse could be correlated with the pupils in some way. However, in normal, alert individuals there is no coordination between spontaneous pupillary movements on one side and pulse and respiration on the other, at least not to a degree discernible by simultaneous recording of these functions. Further, no sympathetic action potentials were found in the cervical sympathetic or long ciliary nerves to the eye in step with those related to breathing that were picked up from the splanchnic nerves of intact animals (Bonvallet and Zbrozyna, 1963). Whether some more subtle kind of correlation can be established by time-locked computer analysis and statistical procedures remains to be seen. But for practical purposes, it can be said with confidence that there is no direct one-to-one relation of cause and effect between respiration or pulse and pupillary movements, as has been claimed. In contrast, under conditions of depressed brain activity, as in some individuals during sleep, in some animal species during hibernation, and in both animals and man in pathologic states that lower general activity and cerebral function, rhythmic groupings of pulse and respiratory waves develop. These are associated in their time pattern in a direct or a more complex way; and in some cases the pupils also oscillate in step. The most common of these conditions, the phenomenon of Cheyne-Stokes breathing, is described in the FLOW +PRESSURE clinical portion of this book. It consists of periodic phases of increasing and decreasing breaths, with interposed phases of respiratory arrest. In many of these patients (but not in all) the pupils dilate during periods of increasing respiratory activity and then slowly contract during periods of waning breaths, to become quite small during the apnoeic pauses. Experimentally, similar patterns of respiration have been elicited in some susceptible human subjects and in animals by forced hyperventilation; by reduction of cerebral blood flow due to loss of blood, impairment of the heart, or occlusion of blood vessels; by anoxia or asphyxia, or by decreased whole body or brain temperature; by poisoning with narcotics or other drugs such as morphine, chloral, strychnine, and muscarine; and by certain brain lesions ( decerebration in frogs, or medullary lesions in mammals). The physiologic mechanism of the vasomotor and respiratory systems, their interaction, and their relations to other systems are too complex to be discussed here (Figure 2-2 and Table 2-1). For our purpose it suffices to know that there are two additional well-known patterns of associated respiratory and blood pressure waves that sometimes are accompanied by pupillary oscillations. They have been classified as "Traube-Hering" waves, which show a one-to-one relation between individual breaths and blood pressure waves (Figure 2-3,A), and "Meyer" waves, in which the blood pressure oscillations are slower, bridging many breaths (Figure 2-3,B). Under clear-cut laboratory conditions and in otherwise healthy animals, Traube-Hering waves usually are produced by asphyxia and Meyer waves by hemorrhage. But there are also intermediary waves, and one type of wave can turn into the other in the same animal and in the same BARORECEPTORS :1 f u "' "' i., X ~-VA_s_o11_o_TO_R_C_EN_TE_R_~~' 0:: I u ... .. 0:: "' if SYMPATHETIC NERVES tI I y RESPIRATORY CENTER PHRENIC NERVES r MEAN BLOOD PRESSURE r RESPIRATION A__A____A__J\ ii: ~ LUNG STRETCHRECEPTORS VENTILATION Figure 2-2. Schematic representation of blood pressure and respiratory control. Note that complex interactions take place between peripheral chemoreceptors, baroreceptors, and lung stretch receptors, central chemoreceptors, and the vasomotor and respiratory centers. The central vasomotor and respiratory neurons are drawn as grouped in "centers" merely for the clarity of the diagram. These cells may exist in diffuse networks. (From N.S. Cherniak, N.H. Edelman, and A.P. Fishman,Amer. J. Physiol.,217 [1969):1375) MEAN @ BLOOD / PRESSURE RESPIRATION _.,..-------... ' MAN\MAAMAA Figure 2-3. Respiratory and blood pressure waves. A: Schematic representation of the relationship between blood pressure and breathing during Traube-Heringwaves, showing a rise and fall of blood pressure between individual breaths. B: Jn Mayer waves the intervals between peaks of blood pressure waves are much longer than those of breaths, so that many respiratory cycles are spanned by each blood pressure wave. (From N.S. Cherniak, N.H. Edelman, and AP. Fishman,Amer. J. Physio/.,217 [1969):1375) 2. SpontaneousPupillaryChanges in Darkness Table 2-1. - YEAR Respiratory, cardiovascular, and pupil oscillations: Literature reviewed AUTHOR RELATED SYSTEMS Vigouroux 1863 ~ Leyoen Heidenhain 1871 Filehne (G) 1873} Filehne (G) 1874 1878 Mosso Langendorff 1881 1881 Leeser Fano 1884 1884 Smirnow respiration - pupil respiration - pupil resEiration - blooa pressure respiration - carcliovas cular function - pupil breatliing - hibernation breathing - carcliovascular breathing - pupil breathing - temperature breathing - cardiovasc. - pupil 1884} 1886 1888 Mosso respiratory Marckwald (G) TuKe Mac Leoa Griffith & Gordon (G) Strughold (B) breathing & pulse - sleep respiration - pupil oreatliing - carcliovascular Traube-Hering waves attention respiratory cycles - tenoon reflexes respiratory cycles - proprio ceptive reflexes mz1921 1924 1929 --- 1929} 1931 King, Blair & Garvey l~~g} Anrep &al Bolton &al O'Hare 1936 1954 --- 1957 1958 --- 1960 1960 --1963 / 79 Tang &al (B) Lacey & Lacey Koizumi & al Koepchen &al Birren & al (B) - cardiovascular breathing - heart rate ins12iration - vasoconstr1ciion visual & auditory reaction timephases of EEG rhythm breathing - vasomotor activity autonomic fluctuations - impul sive striate muscle function muscle afferents - breathing central excitability - reflexes, breathing & pulse frequency cardiac cycle - reaction time YEAR AUTHOR 1963 1963} 1963 1963 --1965 1965 1966} 1967 1967 1967 1968 1969 --1969 1969 1970 --1970 1970 --1971 1973} 1975 -1982 Bonvallet & Zbrozyna Engle Hildebrandt & Engle Koizuma & Suda Forsyth (B) RELATED SYSTEMS resp1·ratory _ cardiovascular .1 central integration - pupi respiratory rhythm reaction time cerebellar and autonomic discharges blood pressure - voluntary behavior Requin & al (B) motor latency - cardiac cycle cycle timing of Golenhofen & respiratory light reflexes . Petranyi breathing - abdommal Okada & sympathetic discharg~s Fox breathing EKG - EUEll Sato pulse _ respiratory rhythm Hagbarth & striated muscle bursts Vallbo Cherniak & al vasomotor waves - phrenic nerve activitv Hukuhara &al breathing - activity of brain stem reticular core cervical sympathetic stimuMills lation - breathing &Sam~on caroiac and splanchnic nerve Cohen & activity Gootman - pupil v. Pierau & al resEiration breathing - pulse Schmidt-vanderheyden &al breathing - circulation Manoach &al (B) respiratory & cardiovascular Borgdorff periodicity - pupil pupil oscillations - heart rate Daum &Fry G = cited after Gilbert, 1892; B = cited after Borgdorff, 1975; see also the sections on fluctuations latent periods in Chapter 3, as well as "pupillary unrest" and "hippus". experiment (see especiaJly Cherniak and co-workers, 1969). Petranyi and Golenhofen (1966, 1967) described changes in the light reflex dynamics during voluntary slowing of respiration as well as during the normal breathing cycle. But they said that the latent period of the reflexes was prolonged and the extent reduced while the contraction was accelerated. This appears very odd, since in our experience a prolonged latent period and reduced extent invariably go with slowing, not with acceleration, of the movement. Pierau and his co-workers recorded pupillary oscillations in pigeons whose heads or midbrains were cooled. These waves corresponded with individual breaths and thus resembled the Traube-Hering type of waves. Borgdorff observed the same reactions in cats and dogs; and he analyzed their mechanism in an admirably lucid and complete series of experiments (summarized in Table 2-2 and Figure 2-4). These experiments showed that (a) pupillary oscillations in step with breathing occur in deeply tranquilized or lightly anesthetized animals, but not in normal, alert animals, nor in deep narcosis (points 1 to 3 in Table 2-2, and Figure 2-4,A); - of pupillary (b) under the conditions of the experiment, that is, with pupillary sympathetic activity blocked by light anesthesia, the pupillary oscillations are due to increasing and decreasing inhibition of the parasympathetic outflow to the eye ( points 4 to 6 in Table 2-2 and Figure 2-4,B and C); (c) movements of the lungs, that is, inspiration and expiration, are not by themselves responsible for pupillary oscillations, first, because their phase relation shiftsbetween natural and artificial breathing (point 7 in Table 2-2); and second, because the pupillarywaves continue without breathing ( points 8 and 10 in Table 2-2 and Figure 2-4,D), while artificial ventilation alone does not produce them (point 12 in Table 2-2 and Figure 2-4,F); (d) both rhythmic activity of the respiratory center and rhythmic variations of blood pressure can elicit pupillary oscillations (points 8, 9, and 10, respectivelyin Table 2-2, and Figure 2-4,D and E). (e) the blood pressure changes also do not affect the ~upils directtr,. that is, by a peripheral vascular effect up?n the _ms,but do so indirectly by a central mecharnsm, tnggered by afferent stimuli from baroreceptor organs in the great vessels (point J1 in Table 2-2), and finally; (f) intermittent electric stimulation of the pulmonary vagus nerves also can cause pupillary 80 / I. Anatomy and Physiology Figure 2-4. Origin of spontaneous pupil movements related to breathing and blood pressure. (From P. Borgdorff,Amer. J. Physiol., 228 [1975):1094) B ARTIFICIAL RESPIRATION tin ♦ A ARTIFICIAL ex RESPIRATION l 2 .Omm tin • ex 1.5 l 4.9 mm 4.5 I I I I I II I I I I I I 11I I I I I 11I I I I I II llh sec A: Normal pupillary unrest without synchrony between pupil and respiration. C ARTIFICIAL SYMPATHICOTOMY RESPIRATION ♦ in ♦ ex 11111111111111111111111111111111111111 sec B: Pupillary oscillations synchronous with breathing cycle had developed in a lightly anesthetized cat. At the arrow the sympathetic chain was cut. This had no effect upon the pupillary oscillations. D ARTIFICIAL RESPIRATION t in BLOOD ---------• PRESSURE ex \-~-] ___ ..,~ l 1,9 uun J500 lux LIGHT !1111111111 I1111111111111111 IIIllIllIIIllI11((((((IIIII((IWI 1,6 sec PHRENIC DISCHARGJS I ••••• I I I I I 111111111111111111 l 2.21Dll l 15 µV I 11111111 l sec D: Pupillary oscillations in step with (central) phrenic nerve discharges continued when artificial respiration was stopped. F 1.8 l NERVE t t t •• C: Suppression of respiratory pupillary rhythm by increasingly bright light (as indicated by the event marker). E :~;DID Hg ARTIFICIAL RESPIRATION t in 165 • ex mmHg 100 BLOOD .......... PRESSURE .tz PW tAIR PHRENIC NERVE ppP13 11:::::n Ill II M CHAMBER OPENED PUPIL 5.5 l ] 50 µV ARTIFICIAL AA RESPIRATION 11 It I 11 It t I 1111 t I I I I I I I' t I I I I I I 111111 sec E: With phrenic nerve discharges abolished by previous hyperven- tilation, and artificial respiration stopped, the pupils followed artificial variations in blood pressure. mm 5. I tin JV\------------- ♦ ex ] 140 I 00 mm Hg PHRENIC NERVE ---------------] 50 µV If I II III I II I I I I I I I I II II1 sec F: Lung movements caused pupillary oscillations after pharmaco- logic suppression of the respiratory center (left side of trace). These effects were abolished when blood pressure was stabilized by introduction of an open air chamber in the carotid blood supply (right side). 2. Table 2-2. literature Pupillary change related to br athing and blood pres YEAR AUTHOR 1866 Leyden (G) 1874 Filehne (G) ~,+=:-;------1 1884 Smirnow (G) ;;-;;-;;;---l--=:-----,-,-.----1 1963 Bonvallet & Zbrozyna 1966 1967 1969 1970 1974 1975 Petr1nyi and Golenhofen; Golenhofen & Petranyi Hukuhara & al v. Pierau & al pontaneous Pupillary Changes in Darkness U re: I 81 Animal experiments described in the EXPERIME 'TAL PROCEDURES A D PUPILLARY ACTIVITY . h -Stokes-like breathing, accompamed abnormally raised blood pressure brought _o~ C ?yne i ence and upils" by rhythmic changes in "sensitivity_, mobi_1i7' occlusionpot cerebral blood flow produced Cheyne-Stokes -like brea th 1I1gb! m er. u illar oscillations (carotid compression in rabbits) , ~soci_ated_t:i~;§ _!I117 { sulphuretted hyarogenff, thi periodic breathing elicited by ?r~ ng air wi d corneal seDBitivity accompanied by waves of pupil size, pulse rate, and ervical s pathetic nerves and recorded action potentials in cats from ~planc~ictoan ~-18 charge:7in conscious cats) in from long ciliary nerves; found rhythDllc respira I')'. . splanchnic nerves but not in cervical chain or long cihary nerves described changes lil human light reflex time-characteristics, synchronous _with respiratory cycles: said active phases were accompanied by prolonged latent periods• reduced amplitude, and increased speed of reflexes r::!f located brain stem reticular neurons that fired in svnchronv wit~ b~eatbin_g . pigeons with head or with midbrain cooled first had m_oderate Ullosis and mcrea~ed light reflexes; with further cooling the pupils enlarged, hght reflexes became sluggish, and respiratory pupillary oscillations anneared . . . . . found nuctuations in pulse- and respiratory rhythms, together w1.th pupUlary oscillat1.0ns. Borgdorff: analysis of they were related as follows respiratory, 1. in alert animals (6\ the ouoils were medium in size and showed normal unrestvasomotor, 2. in conscious cats in deep ether (3) or halothane (7) or pen to barbital (20) the pupils were and pupil medium in size (ether, halothane) or miotic (barbiturate) and did not oscillate oscillations lFhmre 2-4 A)· in cats (num - 3. in light pentobarbital (2), halothane (108) or 20 mg/kg librium (2) the pupils _we1;e 2-5_mm ber of in size and oscillated in step with respiration:f on inspiration and +on expirat1.0n (Figure 2-4 m, animals in each -1. sympathectomy or 10'1 guanethidine eyedrops (14), sympathetic stimulation or 1% arterenol experiment evedroPS (1-1) did not affect the pupillary oscillations ( see Fi11:ure 2-4, B): in brackets) 5. 1 homatropine eyedrops (14) abolished the respiratory pupil oscillations; 6. bright light (7) or o. 25'~ physostigmine eyedrops (7) caused miosis and reduced or abolished the pupillary oscillations (Figure 2-4, C) ; restoring pupil size by sympathetic stimulation points 1, 2, 3 did not bring the pupillarv oscillations back / = thev were not due to miosis per se\. define 7. succinyl choline paralysis with artificial respiration was accompanied by pupillary osciltriggering con- lations , but the phase was shifted: f in exsufflation, and • in insufflation, ditions; b. upon arrest 01 artincta.J. respiration (14) the pupillary oscillations continued in step with central respiratory discharges in the phrenic nerve , without oscillations of blood pressure points -1, 5, 6 or lune: movement (Fi<T11re2-4. D\, explain the 9. oscillations in condition 8 did not develop when the central respiratory discharges were efferent suppressed bv Previous hvoerventilation or by infusion of THAM* (14) . mechanism; 10. but under conditions as in 9 artificial blood pressure changes (by alternate infusion and withdrawal of blood) caused pupillary oscillations (see Figure 2-4, E); points -13 11. the effect of blood pressure variations as in 10. was abolished by denervating the peripheexplain the ral oressure receptors in the carotid and aortic bodies and subclavian arterv~ mechanism 12. artificial ventilation in conditions as in 10. also caused pupillary oscillations; but this of origin effect was indirect, by way of blood pressure changes: it was prevented when the blood pressure changes were prevented by an open-air-chamber interposed in the carotid artery BUPPlv /Fie:ure 2-4 F): 13. when both cent~l respiratory rhythm and blood pressure changes were prevented by THAM· and air-chamber, respectively, electric stimulation of the lung afferents dilated the pupils and intermittent stimulation caused pupillary oscillations *TIIAl\1 - (tris (hydroxymethyl) amino methane), a CO2 buffer; THAM and previous hyperventilation spontaneous rhythmic activity of the respiratory center. (G) = cited after Gibson, 1892. abolish 82 / I. Anatomy and Physiology dilations, even when these are missing when the lungs are inflated pa sively by artificial ventilation (point 13 in Table 2-2, and (c) above). The reason for this lack of influence of artificial respiration in the presence of effective electric stimulation of the same afferent system is not clear. Borgdorffthought it might have been due to the conditions of his experiments. Three separate factors concerned with breathing and cardiovascular rhythms thus can trigger pupillary oscillations: (1) intermittent stimulation of pulmonary afferent fibers, (2) intermittent stimulation of va cular pressure receptors, and (3) firing of central respiratory neurons in the medulla. How can these different impulses all affect the pupils? As described in some detail in Chapter 9, all afferent tracts, in addition to their specific sensory messages to corresponding areas of the brain, send nonspecific impulses by way of collateral fibers to the reticular core of the brainstem. The reticular formation, in turn, has complex afferent and efferent connections to the forebrain and the spinal cord. Activation of this system sets the stage for the higher nervous functions of the individual, and it modulates all motor output. Impulses from central nuclei (such as the medullary vasomotor and respiratory centers) also reach the reticular formation and can, therefore, also modify the activity of the brain. By this mechanism the respiratory and vasomotor rhythms can, under certain circumstances, be correlated with many other motor, sensory, and central nervous changes, as, for example: the sympathetically mediated peripheral vascular resistance; shivering and the activity of the cardiac vagus; sensory thresholds, and visual, auditory, and motor reaction times; spontaneous motor activity and electroencephalographic waves (Table 2-1). As to the pupillary oscillations, reticular activationtriggered by the mechanisms just described-enlarges the pupils by efferent sympathetic discharges to the dilator muscle and by simultaneous inhibition of parasym- pathetic outflow from the midbrain. And subsequent decrease of reticular stimulation allows the pupils to contract again.2 The pupillary oscillations that accompany the TraubeHering type of one-to-one respiratory-vascular oscillations dealt with by Borgdorff, as well as the Meyer and Cheyne-Stokes types, all owe their origin to the same mechanism (Figure 2-5). The common occurrence of fragmentation of the pathologic Cheyne-Stokes syndrome also does not seem difficult to understand in view of the existence of several complex afferent and efferent connections by which the reticular system becomes effective. The clinical syndrome can occur in individuals with brain dysfunction at various levels and of various extents, and these pathologic processes may involve failure of one and not another of the physiologic mechanisms usually participating in the respiratory cycles. 2. In BorgdorfI's experiments, the sympathetic part of these reactions was suppressed by anesthesia. ,, pupil Figure 2-5. Physiologic paths involved in production of pupil oscillations related to breathing and blood pressure. The hatched area outlines the brainstem reticular formation. It receives afferent input from all sensory tracts as well as from cere?ral nu~ clear mas es; and it is involved in general arousal react1ons_wh1ch are accompanied, in addition to many other e~ects, ?Y l?up1l1ary dilation. This movement consists of sympathetic ~xc1tat10n (abo_lished in Borgdorff's experiments by the anesthesia), together ~1th inhibition of the parasympathetic elierent outflow fr~m the third nerve nucleus. For respiratory oscillations of the pupil, the afferent volleys originate from (1) pulmonary stretch receptors, (2) vascular baroreceptors, and (3) the respiratory_nucleus m the medulla. These periodic oscillations do not occur m nor~al, conscious individuals, or in deep narcosis, but they do in light anesthesia or deep tranquilization. (From P. Borgdorff,Amer. J. Physiol., 228 [1975):1094) blood pressure fluctuations lungmovements