Anatomical substrates of oculomotor control

072

Anatomical

substrates of oculomotor

Jean A Btittner-Ennever* It is convenient

to describe

oculomotor

terms of five to six different with relatively vergence several

research

indicates

eye movement

tegmenti

pontis,

the circuits

appear

types,

In this

in

smooth

pursuit,

to the list, gaze-holding.

that many structures

participate

such as the nucleus

eye fields and pretectum.

to run in parallel

in

reticularis However,

rather than being

integrated.

Addresses Institute

of Anatomy,

Ludwig-Maximilian

University,

Opinion

in Neurobiology

Biology

Ltd ISSN

nr@ OKN OPN PET PMT PPRF

dorsal

terminal

1997, 7:872-879

0959-4388

nucleus

of the accessory

optic

tract

excitatory burst neuron frontal eye field y-aminobutyric acid inhibitory burst neuron interstitial nucleus of Cajal dorsal lateral geniculate nucleus magnetic resonance imaging nucleus nucleus

of the optic tract reticularis pontis caudalis

nucleus reticularis tegmenti optokinetic response omnipause neuron

describe

the

basic

neuro-

converge. Next, we review the neural connections of the pretectum, in particular, the nucleus of the optic tract (NOT), and discuss its association with several different eye movement types, not only the optokinetic response or smooth pursuit. Finally, we consider the advances in the anatomical organization of the eye fields in the cerebral cortex.

circuits

The vestibule-ocular reflex is generated by sensory signals from the labyrinthine canals and otoliths, relayed through the vestibular nuclei to the extraocular motoneurons in cranial nerve nuclei III, IV and VI.

pontis

positron emission tomography cell groups of the paramedian

first

pontis (nrtp) is taken as an example of a structure in which information from several eye movement types appears to

Basic oculomotor

Abbreviations

DTN EBN FEF GABA IBN iC LGNd MRI NOT nrpc

will

A simple description of the premotor circuits for saccadic eye movements is that premotor burst neurons in the paramedian pontine reticular formation (PPRF) activate eye muscle motoneurons during horizontal saccades, whereas those in the rostra1 interstitial nucleus of the medial longitudinal fasciculus (rihlLF) activate the eye muscle motoneurons during vertical saccades. Between saccades the premotor neurons in PPRF and rihILF are inhibited by omnipause neurons (OPNs) in the nucleus raphe interpositus (rip). Burst neurons and omnipause neurons receive afferent control from the superior colliculus (SC), whereas the frontal eye fields (FEFs) of the cerebral cortex appear only to contact the OPNs [S”].

http://biomednet.com/elecref/0959438800700872 0 Current

we

Pettenkoferstrasse

11, D-80336 Munich, Germany *e-mail: [email protected] ‘e-mail: [email protected] Current

review,

anatomical networks controlling each eye movement type, and then examine recent studies on the saccadic circuits in the reticular formation. Nucleus reticularis tegmenti

each

saccades,

response,

added

types,

frontal

neuroanatomy

neural circuitry:

reflex, optokinetic

and, most recently

Current

and Anja KE Hornt

eye movement

independent

vestibulo-ocular

control

tract

PPH riMLF

paramedian pontine reticular formation nucleus prepositus hypoglossi rostra1 interstitial nucleus of the medial

SC

superior

longitudinal

fasciculus

colliculus

Introduction Up to now it has been convenient to divide eye movements into different types (i.e. saccades, vestibuloocular reflex, optokinetic response, smooth pursuit and vergence), and to consider the neuroanatomical circuits generating each type as relatively separate [l,Z]. But as a clearer understanding of the circuits emerges, and with the development of new research techniques ((3.1; N Gerrits, \V Graf, N Yatim, G Ugolini, Sot Neulosci Abstt1996, 22:665), there is a tendency in many of the recent publications to move away from the oversimplification of separate anatomical pathways and to tackle the more complex problems of how and where different eye movement types interact with each other or with other internal neural networks [4*].

The optokinetic responses (OKNs) are elicited by the movement of large visual fields across the retina, which generate responses in the retino-recipient accessory optic terminal nuclei of the mesencephalon: the dorsal, medial lateral and interstitial terminal nuclei (DTN, hITI%, LTN, and ITN). These nuclei, along with NOT in the pretecturn, feed the information into the vestibular-oculomotor circuits through which the OKN is generated. Smooth pursuit pathways receive retinal information through two parallel afferent pathways: a motion-sensitive or ‘magnocellular’ pathway, and a form- and colour- sensitive ‘parvocellular’ pathway. Each pathway projects in parallel through the dorsal lateral geniculate nucleus (LGNd) to the primary visual cortex, and supplies posterior parietal cortical areas with information concerning object motion in space (known as the dorsal stream), in contrast to the inferotemporal region, which is more involved in the analysis of form (i.e. the ventral stream). Descending projections from the posterior parietal cortex terminate in

Anatomical substrates of oculomotor control BOttner-Ennever

the

dorsolateral

pontine

nuclei,

from

which

information

is relayed co the dorsal and ventral paraflocculus and the caudal vermis of the cerebellum. Cerebellar efferents, through intermediate relays to the oculomotor nuclei, then generate smooch pursuit.

and Horn

073

Fiaure 1

(a)

Parasagittal

view

Vergence premotor neurons have been found in the mesencephalic reticular formation dorsal to the oculomotor nucleus, as well as in the pretectum [1,6], and provide the vergence

command

to the oculomotor

nuclei.

In addition to these eye movement types, gaze-holding should be included in the list. Gaze-holding circuits are involved in overcoming the elastic properties of the eyeball in the orbit, and serve to hold the eye in a new position after a quick movement. Like other eye movement types, gaze-holding is also subtended by a relatively separate group of neural circuits involving the velocity-to-position integrator: the interstitial nucleus of Cajal (iC) and nucleus prepositus hypoglossi (ppH), with their reciprocal vestibular and cerebellar connections.

The brainstem Saccadic

premotor

reticular

(b) Lateral view

formation

cell groups

In the PPRF, it has now proved possible co anatomically identify some of the functional subgroups essential for the generation of saccades. Premotor excitatory burst neurons (EBNs) for horizontal saccades form a compact group of medium-sized neurons within the dorsomedial part of rhe nucleus reticularis pontis caudalis (nrpc) that can be identified on ordinary Nissl stained sections; inhibitory burst neurons (IBNs) lie more caudally in the nucleus paragigantocellularis dorsalis [7] (Figure 1). In the rihlLF of monkey, premotor neurons for upward and downward saccades appear to be intermingled [5”,8”], whereas in cat. upward neurons were found more caudally than downward neurons [9’]. The same authors describe a possible correlate for vertical IBi%s in the rihILF using GABA as a transmitter, lvhereas excitation is mediated by glutamate/aspartate to oculomotor neurons [lO”*,ll**]. Inhibitory OPNs in PPRF use glycine as a transmitter [12); their destruction with ibotenic acid results in a prolonged duration and slowing of saccades [13”]. In clinical cases of progressive supranuclear palsy with saccadic disturbances, OPNs were associated with neurofibrillary tangles [ 14”). All saccadic premotor neurons and the OPNs contain the calcium-binding protein parvalbumin. a fact utilized to locate the homologue cell groups in humans [S*‘,lS**]. Pontine long-lead burst neurons have been found within the projection areas of the SC: the dorsomedial part of the nrtp, the nucleus reticularis pontis oralis (nrpo) and its border with the nrpc (Figure 1) [16**]. Finally, the central mesencephalic reticular formation, lateral to the oculomotor nucleus, is an area of the reticular formation that is receiving renewed interest on account of its projections to the SC, which

Current Op~mn

A (a) parasagittal

and (b) lateral view of the macaque

I” Neurobiology

monkey

brain,

showing the anatomical location of some of the cortical fields and bralnstem structures participating in the control of eye movements, and referred

to in the text. al, lateral arcuate

sulcus;

as, superior

arcuate sulcus; cga, anterior cingulate gyrus; cgp, posterior clngulate gyrus; cgs, cingulate gyrus; cs, central sulcus; FST, fundus of the superior

temporal

area; io, Inferior

olive; ip, lntraparietal

sulcus;

L, large saccade region of FEF; LIP, lateral lntraparietal area; Ml, pnmary motor cortex; MST, medial superior temporal sulcus; MT, medial temporal area; nrpo, nucleus retlcularls pontis oralis; pgd, nucleus paragigantocellularis dorsalis; PSR, principal sulcus region; pt, pretectum;

ps, prtncipal sulcus; s, small saccade region

of FEF; Sl, primary sensory cortex; SEF, supplementary eye SMA, supplementary motor area; SP, smooth pursuit region STP, superior temporal polysensory area; Vl, primary visual V3A, parietal visual area V3A; VIP, ventral lntraparietal area; 7, area 7; 19, area 19; Ill, oculomotor nucleus; VI, abducens

could provide the feedback signals models of the saccadic burst generator see [S”]).

field; of FEF; cortex; 5, area 5; nucleus.

essential for some ([ 17.1; for a review,

a74

Motor systems

Saccadic

premotor

connectivity

There have been several studies functional saccadic cell groups long-lead bursters and at least some

on the connectivity of the described above. Pontine

innervate the EBK and OPN areas, of them may provide the long-sought

inhibition of the OPNs during a saccade [16**,18’]. Recent anatomical and physiological studies in cat and monkey revealed differential projections from the SC to the saccadic premotor network in the reticular formation, supporting the concept of a saccade pathway and a fixation pathway [19’]. The caudal third of the SC projects directly to the EBN area, but not to the OPn’s, lvhereas the rostra1 third of the SC sends direct projections to the OPNs, but more sparsely to the premotor burst neurons ((ZO’,Zl’*]; JA Biittner-Ennever, AKE Horn, Y Henn, Sor ~Vewosci Abstr 1997, 23:1297). The identification of accommodation neurons in rostra1 SC adds some indirect support for its participation in fixation [W]. A recent model suggests the interaction of the saccadic and vergence system at the level of the OPNs [6]. An additional role of the SC in slow drifts is being studied by several groups [23’,24,25’]. Slow drifts is a term used for a distinct oculomotor pattern in cats that is intermediate between saccades and pursuit, and serves to correct motor error after a saccade is terminated. The anatomical pathways proposed for the drifts are direct connections between the SC and the abducens nucleus that are provided by the tectoreticulospinal neurons. An alternative hypothesis suggests that the slow drifts may be generated

by the saccade

feedback

circuitry

[26’].

The nrtp is a good example of the increasing recognition of the complexity within oculomotor circuits. It is a precerebellar nucleus composed of several subdivisions; it lies dorsal to the pontine nuclei and is separated from it by ascending and descending fibre tracts. The ventral border of nrtp merges with the pontine nuclei, perhaps even functionally [27-l. Until recently, nrtp was associated with saccades on account of its connections with the SC and FEFs, although distinctly separate OKN regions in nrtp have been recorded by Keller and Crandall (see [l]). Newer data reveals the additional involvement of nrtp in vergence [Z&29], smooth-pursuit-like slow drifts [30”], and even in the stabilization of Listing’s plane [31”]. Gaze-holding

The

iC

premotor

lies

adjacent

circuits

to

riMLF,

eye-movement related neuronal burst-tonic and tonic neurons, vertical and torsional integrator to vertical ocular motoneurons targets of iC are the rihlLF, the spinal cord [33”]. The function neurons in iC is still unclear deficits are present after unilateral [35”,36”]. The ppH, [37*], but

and

contains

several

groups [32]. Presumably, which contribute to the function, project directly [8**]. Other projection vestibular nuclei and the of saccade-related burst [34’]. Different torsional riMLF versus iC lesions

like the iC, is involved in integrator for horizontal eye movements, and

function receives

afferents neurons velocity

from all oculomotor structures project to the SC transmitting signals [38’,39**], suggesting

a feedback Kokkoroyannis of ppH) does

control

of saccades.

It

[32]. In cat, ppH eye position and that it serves as is pointed

et nl. [33”] that iC (the vertical not project to SC, which would

out

by

equivalent make SC’s

role as a feedback of saccades seem less likely. However, lesions of the ppH neurons do not affect saccades, but impair gaze-holding [40**]. A function in gaze-holding is also attributed to a collection of cell groups within the paramedian tract (PhlT) neurons of the pontine and medullary reticular formation. The PhIT cell groups receive a copy of all premotor signals, and they project to the cerebellar flocculus and ventral paraflocculus [41*].

Pretectum The oculomotor functions associated with the pretectum are the generation of OKN, the pupillary light reflex and a more recently recognised role in smooth pursuit eye movements. The pretectal olivary nucleus is essential for the pupillary light reflex [42”,43”], and in the primate, it lies engulfed within the KOT, a structure crucial for ocular following ([44*]; S Yakushin, 11 Gizzi, H Reisine, B Cohen, Sor h’ett?-osci Absfr 1994, 20:772.) There is a mounting interest in the interactions between NOT and the highly structured and complex pretectal olivary nucleus [45”,46”]. The reciprocal connections of NOT to all ipsilateral accessory optic nuclei, and of pretectal olivary nucleus to all contralateral accessory optic nuclei imply a functional interplay between the NOT and pretectal olivary nucleus, possibly associated with the perceived motion (parallax) between a fixated visual object and its visual background [47,48**]. Recent tectum

anatomical studies have concentrated

on the efferents of the preon the optokinetic-related

pathways to ppH, the accessory optic nuclei, the inferior olive, the pontine nuclei and nrtp [49’]. However, a summary of NOT connections shown in Figure 2 makes it clear that NOT projects to all known visuomotor systems, and, in addition, interacts with other neural circuits, such as visual attention [48’*]. It is not yet clear how these connections movements.

are used

to coordinate

the generation

of eye

TWO new and interesting projections from NOT have been reported recently: one is to the magnocellular layers of LGNd, fitting with the role of NOT in visual motion [48”]; the second projection involves a select group of extraocular motoneurons outside the main subgroups of the oculomotor nucleus, previously suggested to participate in convergence [46*-l. As pretectal efferents from the pretectal olivary nucleus are known to control pupillary constriction [43”], a role for the pretectal olivary nucleus/NOT complex in the near-response (pupillary constriction, accommodation and convergence) has been

Anatomical

substrates

of oculomotor

control Biittner-Ennever

and Horn

875

Figure 2

Cerebral cortex

Retina Saccade generatlon Gaze flxatlon

SC / Ocular

3 Visual thalamtc modulation

followlng

VOR adaptation

relay

VOR adaptation r7-j

A simplified diagram of NOT efferents to wuomotor structures, proposlng functIonal roles for the pathways. The pattern of connectiwty lmplles that NOT participates In the control of all the different eye movement types. AON, accessory optic nuclei; dlpn, dorsolateral pontlne nuclei; EW, Edinger-Westphal complex; io, lnferlor olive; Ic, locus coeruleus; Ign, lateral genlculate nucleus; nlll, oculomotor nucleus; pgn, pregenlculate nucleus; ppd, nucleus peripeduncularis; ppt, pedunculopontine tegmental nucleus; rt, thalamlc reticular nucleus.

proposed [46**]: howc\,er, recordings from the pretectal olivary nucleus of the alert monkey have cscludcd ii role for at least the pretect21 Iuminancc neurons in the near-response [42”]. The majority of recent papers make no distinction between DTN and NO’T. Iiowever, they are anatomicall) completely separate structures: DTK receives retinal afferents from the accessory optic tract, and is an accessory optic nucleus: whereas NOT receives retinal afferents through a different pathway the brachium of the SC [48”]. Retinal-slip neurons occur in both NOT and DTN; however. unlike DTN, NOT contains several additional classes of neurons: jerk-neurons, LGKd-projetting neurons (recently confirmed as GAB&positive but calbindinand P”r~“lbumin-negative [SO*]), 2nd two nen NOT cell types (LGNd-projecting-saccade neurons [51*], and omnidirectional pausers [SP]). In the pretectum, the retinal-slip and saccade-related circuitries appear to run in parallel with each other rather than becoming integrated. The repeated misconception that X0-1’ is an accessory optic nucleus has certainly contributed to maintaining the mystery regarding its function.

The pretcctum also projects to the zona incerta. \lay Pt N/. [.5.3**] present 3 careful study of the connectivity of zone incerta to SC and the pretcctum. lvith the salutar) demonstration that its pretcctal affercnts arise from the anterior pretectal nucleus rather than NO’I’. AS some studicb assumed [-KY*]. A contemporary rcpol-t .sho\vs for the first time that there are saccadc-rcl:lted p~tse neurons in the zona incerta [i-l’].

Cortical

eye fields

Initially the FEFs \vrre thought to play ;I role on11 in saccades, but subsequent research has sho\vn that FEFs control gaze-fixation [55]. Now. it is further subdivided into a FEF-pursuit and a l:EF-svccade area (Figure 1). Different retrograde tracers were injected into the FEF-pursuit and FEF-saccadc arcas. and labelling was found in many cortical eye fields (including SEF, LIP, .\lST, PSR; see Figure 1) [56,57**]. Double-labelling experiments demonstrated that each of the above eye fields had two separate nodes of labelling: one cluster labelled from the pursuit area, and the other from the FEF saccade region. implying that the saccadic and the cortical pursuit networks are relatively independent [57**].

076

The

Motor systems

interconnected

cortical

eye

fields

appeared

to be

about the same hierarchical level, based on the criteria that cortico-cortical connections, between complex and less-complex visual processing areas, are evident from the bilaminar V/VI), whereas

References

. l

pattern of terminals (in laminae I and a columnar input, to all layers, indicates a

connection between cortical areas on the same hierarchical level [56,57**]. Some of these studies were carried out in the capuchin (Cebus) monkey, which has been shown to have similar cortical eye fields to those of the macaque [57**,58*]. In humans, independent saccadic-FEFs and pursuit-FEFs could also be distinguished by functional RIRI imaging: they appear to be localized to Brodmann’s area 6, rather than area 8, as in the monkey [59*].

The posterior cingulate cortex (cgp) (Figure l), is usually considered as a limbic area, but experiments in the alert monkey found that single-cell responses are associated with the monitoring of eye movements [60’]. Colleagues from the same group simultaneously published results that indeed act as a warning to the interpretation of cortical responses in alert monkey. They demonstrated, by a variety of ingeniously devised tasks, that attention and anticipation played a major role in unit responses from area LIP in the parietal eye fields (Figure

recorded 1) [61”].

Functional imaging techniques such as PET scans, functional hlRI, or transcranial magnetic stimulation have enabled the cortical eye fields found in monkey to be anatomically visualized for the first time in humans [62]. Unfortunately, interpreting the functional images is often extremely difficult, and is completely impossible in xeroxed articles! However, there have now been several demonstrations of saccade-paradigms enhancing activity in the FEF, the supplementary eye fields, dorsolareral prefrontal cortex, parietal eye fields. posterior parietal cortex and, in some cases, the cingulatr [63*,64*]. whereas smooth pursuit enhances the occipitotemporal cortex [65**].

gyrus lateral

and recommended

Papers of particular interest, published have been highlighted as:

*

reading

within the annual period of review,

of special interest of outstanding interest

1.

Bijttner U, Bijttner-Ennever JA: Present concepts of oculomotor organization. In Neuroanatomy of the Ocu/omotor System. Edited by Biittner-Ennever JA. Amsterdam: Elsevier; 1966332.

2.

Biittner-Ennever JA, Jenkins C, Armin-Parsa H, Horn AKE, Elston JS: A neuroanatomical analysis of lid-eye coordination in cases of ptosis and downgaze paralysis. C/in Neuropathol 1996, 15:313-316.

3. .

Kaufman GD, Mustari MJ, Miselis RR, Perachio AA: Transneuronal pathways to the vestibulocerebellum. I Comp Neural 1996, 370:501-523. A powerful technique (see N Gerrits, W Graf, N Yatim, G Ugolinl, Sot NeurosciAbstr 1996, 22:665) that can effectively reveal crosslinks between neural circuits in the oculomotor system, in which basic pathways are reasonably well understood. 4. .

Vermersch Al, Muri RM, Rivaud S, Vidailhet M, Gaymard B, Agid Y, Pierrot Deseilligny C: Saccade disturbances after bilateral lentiform nucleus lesions in humans. I Neural Neurosurg Psychiatry 1996, 60:179-l 64. Indicates a role of the putamen and globus pallidus in the cortical control of saccades when the experimental paradigm requires the use of an Internal representation of the target, such as in memory-guided or predictive saccades. 5. ..

Moschovakis AK, Scudder CA, Highstein SM: The microscopic anatomy and physiology of the mammalian saccadic system. Prog Neurobiol 1996, 50:133-254. A monumental review of the physlological and anatomical properties of all known functional cell groups associated with saccades. Most of the data are based on the reconstruction of physiologically identified, intracellularly injected neurons in the primate. The authors evaluate several models for saccade generation. 6.

Mays LE, Gamlin PD: Neuronal response. Curr Opin Neurobiol

7.

Horn AKE, Biittner-Ennever JA, Suzuki Y, Henn V: Histological identification of premotor neurons for horizontal saccades in monkey and man by parvalbumin immunostaining. J Comp Neural 1995, 359:350-363.

circuitry controlling 1995, 5:763-766.

the near

6. ..

Horn AKE, BOttner-Ennever JA: Premotor neurons for vertical eye-movements in the rostra1 mesencephalon of monkey and man: the histological identification by parvalbumin immunostaining. I Comp Neural 1997, in press. Identified vertical premotor neurons in the riMLF and IC of monkey, which are medium-sized and parvalbumin-lmmunoreactive. These properties are used to accurately outline the riMLF and iC homologue in humans. 9. .

Conclusions In conclusion, recent investigations of the anatomical substrates of oculomotor control reveal that in several structures, such as the FEFs of the cortex, the pretectum and nrtp, more than one type of eye movement is represented (e.g. saccades, smooth pursuit, vergence or OKN). However, the circuits remain relatively separate from each other at these levels, indicative of parallel processing.

Acknowledgements This work was supported (SFU 462; 03).

1)~ the

Deurxhc

F[,rschung\gcmclnschafr

Wang SF, Spencer RF: Spatial organization of premotor neurons related to vertical upward and downward saccadic eye movements in the rostra1 interstitial nucleus of the medial longitudinal fasciculus (riMLF) in the cat. / Comp Neural 1996, 366:163-l 60. Small biocytin injections into different regions of the riMLF In cat suggest a tendency of premotor upward-neurons to lie more caudally and downwardneurons to lie more rostrally. 10. ..

Wang SF, Spencer RF: Morphology and soma-dendritic distribution of synaptic endings from the rostra1 interstitial nucleus of the medial longitudinal fasciculus (riMLF) on motoneurons in the oculomotor and trochlear nuclei in the cat J Comp Neural 1996, 366:149-l 62. Using double-labelling methods in combination with electron microscopy, the authors studied the morphology and distribution of synaptic terminals from riMLF afferents at the vertical eye muscle motoneurons. They showed that the same riMLF region contacts the motoneurons by excitatory and inhibitory boutons mainly at the proximal and distal dendrites. The innervation pattern from riMLF afferents is compared to the vestibular inputs to oculomotor neurons and was found to be different in morphology, mode, and soma-dendritic location. 11. ..

Spencer RF, Wang SF: lmmunohistochemical localization of neurotransmilters utilized by neurons in the rostra1 interstitial nucleus of the medial longitudinal fasciculus (riMLF) that

Anatomical

substrates

of oculomotor

control

BOttner-Ennever

and Horn

a77

22. .

project to the oculomotor and trochlear nuclei in the cat. J Camp Neurool 1996, 366:134-l 48. Using double-labelling methods in combination with electron microscopy, the authors show in the cat that synaptic endings in the oculomotor and trochlear nucleus, which were anterogradely labelled from riMLF, are GABA-, glutamate- or aspartate-immunoreactive.

Sato A, Ohtsuka K: Projection from the accommodation-related area in the superior colliculus of the cat J Comp Neural 1996, 367:465-476. An interesting physiological-anatomical study of superior colliculus efferents. However, the authors’ location of the nucleus raphe interpositus (rip) is incorrect.

12.

23. .

Horn AKE, Biittner-Ennever JA. Wahle P, Reichenberger I: Neurotransmitter profile of saccadic omnipause neurons in nucleus raphe interpositus. J Neurosci 1994, 14:2032-2046.

13. ..

Kaneko CRS: Effect of ibotenic acid lesions of the omnipause neurons on saccadic eye movements in Rhesus macaques. J Neurophysiol 1996, 75:2229-2242. A chemical lesion study with careful histological controls demonstratmg a decrease in peak saccadic velocity and increase in saccade duration, but no impairment of fixation, after damage of the omnipause neurons.

Grantyn AA, Dalezios Y, Kitama T, Moschovakis AK: Neuronal mechanisms of two-dimensional orienting movements in the cat 1. A quantitative study of saccades and slow drifts produced in response to the electrical stimulation of the superior colliculus. Brain Res Bull 1996, 41:65-82. A complementary study to (241, supporting the hypothesis that slow postsaccadic eye movements can result from excitation of tectoreticular neurons directly on abducens motoneurons and an indirect oligosynaptic pathway, not involving the saccadic burst generator. 24.

14. ..

Revesz T, Sangha H, Daniel SE: The nucleus raphe interpositus in the Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy). Brain 1996, 119:l 137-l 143. This is a careful morphometric analysis of an identified cell group, the omnlpause neurons, in clinical cases of progressive supranuclear palsy with and without eye movement disturbances. It shows the omnipause neurons are more severely affected in cases with eye movement deficits (i.e. they are reduced in number and exhibit neurofibrillary tangle formation) than in cases without eye movement deficits. 15. ..

Horn AKE, Btittner-Ennever JA, Biittner U: Saccadic premotor neurons in the brainstem: functional neuroanatomy and clinical implications. Neuro-Ophthalmol 1996, 16:229-240. A review of the identification of functional premotor cell groups of the saccadic system in humans. 16. ..

Scudder CA, Moschovakis AK, Karabelas AB, Highstein SM: Anatomy and physiology of saccadic long-lead burst neurons recorded in the alert squirrel monkey. II. Pontine neurons. J Neurophysiol 1996, 76:353-370. This is the first detailed description of the projection targets of physlologlcally identified saccadic long-lead burst neurons (LLBNs) in the pontlne reticular formation using intra-axonal HRP-injections in the pnmate. Three types of LLBNs were reconstructed: precerebellar LLBNs in the nucleus reticularis tegmenti pontis (nrtp), reticula-spinal LLBNs in the excitatory burst neuron (EBN) area and pontine LLBNs in the nucleus reticularis pontis oralls with projections to the EBN and omnipause neuron area. The combination of detailed anatomy and physiology in this type of study IS invaluable for further progress in understanding the brainstem control of saccades. 1 7. .

Waitzman DM, Silakov VL, Cohen B: Central mesencephalic reticular formation (cMRF) neurons discharging before and during eye movements. J Neurophysiol 1996, 75:1546-l 572. A physiological characterisation of neurons in the cMRF suggesttng an important role in saccades, providing the superior colliculus with tnformatlon on the current eye displacement during a saccade. 18. .

Kamogawa H, Ohki Y, Shimazu H, Suzuki I, Yamashita M: Inhibitory input to pause neurons from pontine burst neuron area in the cat. Neurosci Leff 1996, 203:163-l 66. A specific area of nucleus reticularis pontis caudalis within the excitatory burst neuron area, purported to contain long-lead burst neurons, was found to be the most effective site from which omnipause neurons could be inhibited by electrical stimulation. 19. .

Munoz DP, Waitzman DM, Wurtz RH: Activity of neurons in monkey superior colliculus during interrupted saccades. J Neurophysiol 1996, 75:2562-2580. A stimulation and recording study in the superior colliculus (SC) of monkey suggesting that fixation cells in the rostra1 SC inhibit burst and build-up neurons in the caudal SC. 20. .

Chimoto S, lwamoto Y, Shimazu H, Yoshida K: Functional connectivity of the superior colliculus with saccade-related brain stem neurons in the cat Prog Brain Res 1996, 112:157165. An electrophysiological study in the cat showtng that stimulation of the caudal superior colliculus (SC) activates premotor burst neurons at monosynaptic latencies, which do not respond to stimulation of the rostra1 SC. Stimulation of the rostra1 SC activates ommpause neurons directly, which are inhibited after stimulation of the caudal SC. 21. ..

Scudder CA, Moschovakis AK, Karabelas AB, HIghstein SM: Anatomy and physiology of saccadic long-lead burst neurons recorded in the alert squirrel monkey. I. Descending projections from the mesencephalon. J Neurophysiol 1996, 76:332-352. An excellent intracellular-HRP-injection study of physiologically Identified mesencephalic long-lead burst neurons showing for the first time the projection targets within the paramedian pontine reticular formation.

Olivler E, Grantyn A, Chat M, Berihoz A: The control of slow orienting eye movements by tectoreticulospinal neurons in the cat-behavior, discharge patterns and underlying connections. Exp Brain Res 1993, 93:435-449.

25. .

Missal M, Lefevre P, Delinte A, Crommelinck M, Roucoux A: Smooth eye movements evoked by electrical stimulation of the cat’s superior colliculus. Exp Brain Res 1996, 107:382-390. Another study about slow eye movements atter stlmulatton of the supenor colliculus (see [23’]) examining the effects of stimulation parameters upon movement velocity. 26. .

Breznen B, Lu SM, Gnadt JW: Analysis of the step response of the saccadic feedback system: behavior. Exp Brain Res 1996, 111:337-344. This paper proposes an alternative hypothesis for the generation of slow eye movements after prolonged stimulatton of the superior colliculus. 2 7. .

Schwarz C, Thler P: Comparison of projection neurons in the pontine nuclei and the nucleus reticularis tegmenti pontis of the rat J Comp Neural 1996, 376:403-419. A useful double-labelling technique for studying the detailed morphology of retrogradely identified neurons, and applied here to an area of high Interest. 28.

Gamlln PDR, Clarke RJ: Single-unit activity in the primate nucleus reticularis tegmenti pontis related to vergence and ocular accommodation. J Neurophys/ol 1995, 73:21 15-21 19.

29.

Averbuch Heller L, Leigh RJ: Eye movements. 1996, 9:26-31.

Curr Opin Neural

30. ..

Yamada T, Suzuki DA, Yee RD: Smooth pursuit-like eye movements evoked by microstimulation in macaque nucleus reticularis tegmenti pontis. J Neurophysiol 1996, 76:3313-3324. The exact reconstruction of stimulation sites reveal a topography in nrtp in which a new smooth-pursuit-like area lies rostromedially and the saccade-like neurons lie in caudal nrtp. 31. ..

Van Opstal Al, Hepp K, Suzuki Y, Henn V: Role of monkey nucleus reticularis tegmenti pontis in stabilization of Listing’s plane. J Neurosci 1997, 16:7284-7296. This study provides evidence for neural circuits implementing Listing’s law, rather than passive orbital forces -a controversial topic. 32.

Fukushima K, Kaneko CRS, Fuchs AF: The neuronal substrate of integration in the oculomotor system. Prog Neurobiol 1992, 39:609-639.

33. ..

Kokkoroyannis T, Scudder CA, Balaban CD, Highstem SM, Moschovakis AK: Anatomy and physiology of the primate interstitial nucleus of Cajal. 1. Efferent projections. J Neurophysiol 1996, 75:725-739. This is the first anatomical description of efferent pathways of the interstiteal nucleus of Cajal in primate using small tracer injections with Phaseolus lectin and biocytin. It disclosed three projection systems: a commissural, an ascending and a descending pathway. 34. .

Helmchen C, Rambold H, Bijttner U: Saccade-related burst neurons with torsional and vertical on-directions in the interstitial nucleus of Cajal of the alert monkey. Exp Brain Res 1996, 112:63-78. Physiological study of non-premotor saccade-related neurons in the Inter& teal nucleus of Cajal usmg three-dimensional eye movement recordings. The properties are compared to those of saccadic premotor burst neurons in the riMLF. 35. ..

Helmchen C, Glasauer S, Bartl K, Bi.ittner U: Contralesionally beating torsional nystagmus in a unilateral rostra1 midbrain lesion. Neurology 1996, 47:482-486. A small unilateral lesion, thought to affect the nMLF, causes a torsIonal nystagmus to the contralateral side of the lesion, which is the opposite directjon found after a unilateral lesion of the interstitial nucleus of Cajal. A slowing of ipsilaleral torsional fast phases was also seen (see [36”]).

878

Motor

systems

36. ..

Riordan-Eva P, Faldon M, Biittner-Ennever JA, Gass A, Bronstein AM, Gresty MA: Abnormalities of torsional fast phase eye movements in unilateral rostra1 midbrain disease. Neurology 1996, 47:201-207. Small unilateral lesions thought to affect riMLF efferents caused only a slowing of ipsidirectional torsional fast phase eye movements. Compare with [35”]. 37. .

Godaux E, Cheron G: The hypothesis of the uniqueness of the oculomotor neural integrator: direct experimental evidence in the cat. / Physiol Land 1996, 492:517-527. A recording study in the prepositus nucleus of the cat that favours the hypothesis of a unique horizontal oculomotor integrator. 38. .

Hardy 0, Corvisier J: Firing properties of preposito-collicular neurones related to horizontal eye movements in the alert cat tip Brain Res 1996, 1 lo:41 3-424. A recording study demonstrating that preposito-collicular neurons code eye position and eye velocity just like eye muscle motoneurons, suggesting a role In feedback control of an ongoing saccade. 39. ..

Corvisier J, Hardy 0: Topographical characteristics of prepositocollicular projections in the cat as revealed by Phaseolus vulgaris-leucoagglutinin technique. A possible organisation underlying temporal-to-spatial transformations. fwp Brain Res 1997, 114:461-471. An anatomical tracing study, which shows that the preposito-collicular (see [38’]) projection is organized in two axonal trajectories; in addition, the projectron is weighted along the rostrocaudal axis of the contralateral superior colliculus. 40. ..

Kaneko CRS: Eye movement deficits following ibotenic acid lesions of the nucleus prepositus hypoglossi in monkey. I. Saccades and fixation. I Neurophysiol 1997, 78:1763-l 768. A chemical lesion study of the prepositus nucleus (ppH) with careful histological controls of the damage, demonstrating only minor deficits in gaze holding, no changes of saccades, but impairment of the fixation ability. This paper favours the existence of multiple neuronal Integrators rather than of a single multipurpose element (see [37’]), and it contradicts models that rely on feedback control from the ppH (see [36’,39”1). 41.

Biittner-Ennever JA. Horn AKE: Pathwavs from cell arouos of the paramedian tr&ts to the floccula; region. Ann-NYkcad SC; 1996, 761:532-540. This study demonstrated for the first time the route taken by the paramedian tract (PMT) neurons efferents in the external arcuate fibres to the flocculus and ventral paraflocculus. The PMT cell groups receive inputs similar to the extraocular motoneurons, and could provide the cerebellum with a motor error feedback signal.

.

42. ..

Zhang H, Clarke RJ, Gamlin PDR: Behavior of luminance neurons in the pretectal olivary nucleus during the pupillary near response. fxp Brain Res 1996, 112:156-l 62. Shows luminance neurons In the pretectal olive do not fire with the pupillary constriction accompanying the near-response. This finding is a clear answer to the hypothesis that this nucleus might be involved in the near-response (see [46”1). It remains to be seen what neural elements in this region are associated with the small motoneurons of the oculomotor nucleus. 43. ..

Kourouyan HD, Horton JC: Transneuronal retinal input to the primate Edinger-Westphal nucleus. J Comp Neurol 1997, 381:68-80. A satisfying demonstration of the retinal input through the pretectal olive to the Edinger-Westphal complex with [3H]proline, and a critical account of terminology of the area. 44. .

llg UJ, Hoffmann KP: Responses of neurons of the nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic tract in the awake monkey. fur J Neurosci 1996, 8:92-l 05. Single-cell recording analyzing the role of NOTlDTN in optokinetlc and smooth pursuit eye movements. Unfortunately, no differentiation between NOT and DTN was made. 45. ..

Klooster J, Vrensen GFJM: The ultrastructure of the olivary pretectal nucleus in rats. A tracing and GABA immunohistochemical study. Exp Brain Res 1997, 114:51-62. A technically excellent study of the complex structure of the pretectal olive. 46. ..

Btittner-Ennever JA, Cohen B, Horn AKE, Reisine H: Pretectal projections to the oculomotor complex of the monkey and their role in eye movements. J Comp Neural 1996, 366:346359. Pretectal projections to a specific set of oculomotor motoneurons (c-group) are verified with transsynaptic retrograde tracer, and suggest a role of the pretectum in the near-response. This is the first attempt to correlate the function of two closely associated components of the pretectum: the NOT and the pretectal olivary nucleus.

47.

Miles FA: The sensing of rotational and translational optic flow by the primate optokinetic system. In Visual Marion and Its Role in the Stabilization of Gaze. Edited by Miles FA, Wallman J. Amsterdam: Elsevier; 1993:393-403.

48. ..

Biittner-Ennever JA, Cohen 8, Horn AKE, Reisine H: Efferent pathways of the nucleus of the optic tract in monkey and their role in eye movements. I Comp Neurol 1996, 373:90-l 07. A functional analysis of the efferent pathways from NOT, demonstrating that it projects to structures involved in the control of six different types of eye movements. It is suggested that, under the control of the cerebral cortex, NOT could function as a coordinator of the oculomotor circuits to generate the appropriate motor response. The paper emphasizes the importance of considering NOT and DTN as functionally separate structures. 49. .

Vargas CD, Volchan E, Nasi JP, Bernardes RF, Rochamiranda CE: The nucleus of the optic tract (NOT) and the dorsal terminal nucleus (DTN) of opossums (Didelphis marsupialis aurita). Brain Behav ho/ 1996, 48:1-l 5. A comparison of pretectal cell groups with commissural or Inferior olive projectrons in the opossum. NOT and DTN differ, but are considered as a complex. 50. .

Reimann S, Schmidt M: Histochemical characterisation of the pretecto-geniculate projection in kitten and adult cat Dev Bra/n Res 1996, 91 :143-l 48. Thrs study shows that 50% of the pretecto-geniculate projection neurons are GABAergic, but no projection neurons are calbindin- or parvalbuminImmunoreactive. 51. .

Schmidt M: Neurons in the cat pretectum that project to the dorsal lateral geniculate nucleus are activated during saccades. J Neurophysiol 1996, 76:2907-2918. Description of a new group of cells in NOT and posterior pretectal nucleus that fire with saccades in the light and darkness (in contrast, the jerk neurons fire only with saccades in light). Unfortunately no differentiation between NOT and DTN was made. 52. .

Mustari MJ, Fuchs AF, Pong M: Response properties of pretectal omnidirectional pause neurons in the behaving primate. J Neurophysiol 1997, 77:116-l 25. Description of the physiological properties of a new cell group type in the pretectum that pauses after all saccades.

53. ..

May PJ, Sun W, Hall WC: Reciprocal connections between the zona incerta and the pretectum and superior colliculus of the cat. Neuroscience 1997, 77:1091-l 114. This paper IS a comprehensive study about the connectivity of the zona lncerta (zi), with the superior colliculus and pretectum using tracer methods combined with electron microscopy. The study revealed projections from the intermediate layers In the superior colliculus to the zi, supporting Its involvement in control of saccades (see [54-I). A stronger incertotectal pathway was shown to originate primarily from the ventral subdivision of ZI. From the pretectum, mainly the anterior pretectal nucleus sends an excitatory projection to the ventral zi. 54. Ma TP: Saccade-related omnivectoral pause neurons in the . primate zona incerta. Neuroreporf 1997, 7:2713-2716. This is the first detailed descnption of another saccade-related group of pause-neurons in the zona incerta of monkey. These cells show a similar firing pattern during saccades as the omnipause neurons in the nucleus raphe interpositus, but they have direct probably GABAergic projections to the superior colliculus (shown in [53”]). 55.

Dias EC, Kiesau M, Segraves MA: Acute activation and inactivation of macaque frontal eye field with GABA-related drugs. J Neurophysiol 1995, 74:2744-2748.

56.

Stanton GB, Bruce CJ, Goldberg ME: Topography of projections to posterior cortical areas from the macaque frontal eye fields. J Comp Neural 1995, 353:291-305.

57. ..

Tian JR, Lynch JC: Corticocortical input to the smooth pursuit and saccadic eye movement subregions of the frontal eye field in Cebus monkeys. J Neurophysiol 1996, 76:2754-2771. The authors demonstrate that the smooth pursuit-frontal eye field (FEF) area and saccadlc-FEF area have separate afferent sites within the other cortical eye fields. The results imply the parallel flow of smooth pursuit and saccadlc information in the cortex rather than a convergence of information. The cebus and macaque monkey have similar cortical eye fields. Leichnetz GR, Gonzalo-Ruiz A: Prearcuate cortex in the Cebus monkey has cortical and subcortical connections like the macaque frontal eye field and projects to fastigial-recipient oculomotor-related brainstem nuclei. Brain Res Bull 1996, 41 :l -29. A comprehensive documentation of cortical and subcortlcal connections of the prearcuate cortex (the putative homologue of the frontal eye field) using horseradish peroxidase tracing. 58. .

Anatomical

59. .

Petit L, Clark VP, lngeholm J, Haxby JV: Dissociation of saccaderelated and pursuit-related activation in human frontal eye fields as revealed by fMRI. J Neurophysiol 1997, 773386-3390. The study confirms the location of frontal eye fields (FEFs) I” humans and provides evidence for subdivisions into a pursuit and saccade area. Olson CR, Musil SY, Goldberg ME: Single neurons in posterior cingulate cortex of behaving macaque: eye movement signals. J Neurophysiol 1996, 76:3285-X300. Establishes saccade-related properties of a cortical area associated with spatial analysis of visual images.

60. .

Colby CL, Duhamel JR, Goldberg ME: Visual, presaccadic, and cognitive activation of single neurons in monkey lateral intraparietal area. I Neurophysiol 1997, 76:2841-2852. Provides a clever set of paradigms lo tease out the effects of attention and anticipation on parietal eye field cell responses. 61. ..

62.

Carter N, Zee DS: The anatomical localization of saccades using functional imaging studies and transcranial magnetic stimulation. Curr Opln Neural 1997, 10:10-l 7.

63. .

Sweeney JA, Mintun MA, Kwee S, Wiseman Rosenberg DR, Carl JR: Positron emission

MB, Brown DL, tomography study

substrates

of oculomotor

control

Btittner-Ennever

and Horn

879

of voluntary saccadic eye movements and spatial working memory. J Neurophysiol 1996, 75:454-468. Regions of the cerebral cortex in humans involved in different types of saccadic eye movements are localized with respect to the hand-related motor cortex (used here as a landmark). The results appear in agreement with those found in monkey cortex, but the data are extremely difficult to assess anatomically. 64. .

Petit L, Orssaud C, Tzourio N, Crivello F, Berthoz A, Mazoyer B: Functional anatomy of a prelearned sequence of horizontal saccades in humans. J Neurosci 1996, 16:3714-3726. Excltlng results indicating cortical eye fields, basal ganglia and vermis in internally generated saccade-tasks, but difficult to assess anatomically. 65. ..

Barton JJS, Simpson T, Kirikopoulos E, Stewart C, Crawley A, Guthrie B, Wood M, Mikulis D: Functional MRI of lateral occipitotemporal cortex during pursuit and motion perception. Ann Neural 1996, 40:387-398. A clear discussion on the comparison of human cortical oculomotor functlon with exisrlng results In monkey. The findings show that an area in the lateral occipitotemporal cortex is related to target motion during pursuit eye movements, and could represent the human homologue of MT. However, additional eye-movement-related inputs to this area suggest that MST may also Ile I” the same region.