NOSOLOGICAL ENTITIES?

Psychoanatomical substrates of Blints syndromeM Rizzo, S P Vecera. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

J Neurol Neurosurg Psychiatry 2002;72:162178

Objectives: From a series of glimpses, we perceive a seamless and richly detailed visual world. Cer-ebral damage, however, can destroy this illusion. In the case of Blints syndrome, the visual world isperceived erratically, as a series of single objects. The goal of this review is to explore a range of psy-chological and anatomical explanations for this striking visual disorder and to propose new directionsfor interpreting the findings in Blints syndrome and related cerebral disorders of visual processing.Methods: Blints syndrome is reviewed in the light of current concepts and methodologies of visionresearch.Results: The syndrome affects visual perception (causing simultanagnosia/visual disorientation) andvisual control of eye and hand movement (causing ocular apraxia and optic ataxia). Although it hasbeen generally construed as a biparietal syndrome causing an inability to see more than one object ata time, other lesions and mechanisms are also possible. Key syndrome components are dissociableand comprise a range of disturbances that overlap the hemineglect syndrome. Inouyes observations insimilar cases, beginning in 1900, antedated Blints initial report. Because Blints syndrome is notcommon and is difficult to assess with standard clinical tools, the literature is dominated by case reportsand confounded by case selection bias, non-uniform application of operational definitions, inadequatestudy of basic vision, poor lesion localisation, and failure to distinguish between deficits in the acuteand chronic phases of recovery.Conclusions: Studies of Blints syndrome have provided unique evidence on neural substrates forattention, perception, and visuomotor control. Future studies should address possible underlyingpsychoanatomical mechanisms at bottom up and top down levels, and should specifically considervisual working memory and attention (including object based attention) as well as systems for identifi-cation of object structure and depth from binocular stereopsis, kinetic depth, motion parallax, eyemovement signals, and other cues.

In 1909, Resz Blint described in a German language peri-odical a striking set of visual defects in a man with bilateralhemispheric lesions.1 This Hungarian physician studied hispatient from 1903 until the man died in 1906. The patientsdefects were due to progressive cerebrovascular complicationsthat began in 1894. The symptom complex included:

(1) Spatial disorder of attention: an inability to perceive atany one time the several items of a visual scene. This has beencompared with visual disorientation (Gordon Holmes 1918term)2 and simultanagnosia (defined by Wolpert in 1924 as aninability to interpret the totality of a scene despite preserva-tion of ability to apprehend individual portions of thewhole).3

(2) Psychic paralysis of gaze: an inability to shift gazevoluntarily to objects of interest despite unrestricted eye rota-tions. This resembled later descriptions of spasm of fixation4 5

and acquired ocular apraxia (apraxia, Greek for not acting),but differed from congenital ocular motor apraxia, a childhooddisorder in which head thrusts occur with voluntary refixationdespite a full range of reflexive saccades.6 7

(3) Optic ataxia (ataktos, Greek for disorderly): difficultyreaching under visual guidance despite normal limb strength.This was not due to defective position sense (when Blintpositioned his patients left hand, the man was able to imitatethe movement with his right). Nor was it purely visual, inwhich case both hands should have been affected equally (theright hand was worse).

Blints patient showed signs of a left hemineglectsyndrome: he was unaware when approached from the left orfrom behind, and his focus of attention was skewed 35 to 40degrees into the right hemifield. When encouraged to look tothe left, the man would see objects immediately and always,but attention within this area would quickly wane due to a

concentric constriction of the attentive field.1 Blintattributed the gaze disorder to the attention defect.

The patient had adequate visual acuity (20/20 in the righteye and 20/40 in the left) and visual fields (for white objectsand colours) and could identify a relatively large target (suchas a person) by vision alone, yet could not place a dot in thecentre of a circle or triangle or perceive this error on visualinspection. Blint suggested that his patient could see eitherthe dot or the shape, but could not perceive them both at thesame time. He reasoned that the man could see only oneobject at a time, regardless of the objects size.

Postmortem showed a deformed and atrophic brain, withbilateral and nearly symmetric lesions of the posterior parietallobe, upper temporal lobe, and occipital lobe; marked damagein posterior parts of the superior and inferior parietal lobules;and lesser changes in the left central gyrus and surroundingareas. The left internal capsule was also damaged. There wereno changes in the frontal lobes, optic nerve or tract, lateralgeniculate body, or calcarine cortex. In a famous anatomicalsketch that depicted the lateral surfaces of the patients leftand right hemispheres (fig 1), Blint emphasised the lesionsin the angular gyri and the preservation of the cortex aroundthe calcarine fissure, even though there was clearly damage inother vision related structures (including the posterior corpuscallosum, bilateral white matter, upper portions of thethalami, and the pulvinar).

Gordon Holmes reported on disturbances of visualorientation in six soldiers with occipital wounds whomisjudged the location and distance of an object, and the rela-tive distance between two objects despite adequate visual acu-ity and stereoacuity.2 In 1946, Holmes explained it thus:

See end of article forauthors affiliations. . . . . . . . . . . . . . . . . . . . . . .

Correspondence to:M Rizzo, Professor ofNeurology, Engineering,and Public Policy,University of Iowa Collegeof Medicine, Department ofNeurology, 200 HawkinsDrive, Iowa City, IA522421053, USA;matthew-rizzo@uiowa.edu

Received4 January 2001In final revised form 17September 2001Accepted 20 September2001. . . . . . . . . . . . . . . . . . . . . . .

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As a result of visual disorientation, a patient may beable to find his way about even in familiar surroundings,and owing to the failure to recognise the positions anddistances of objects, he may collide with obstacles, andmay even walk into a wall though he sees it directly. Heis also unable to grasp or point accurately to objectswithin the range of his vision.8

The findings among these soldiers are often compared withthose in Blints case, but also resemble the (heretoforeneglected) findings in soldiers studied by Tatsuji Inouye, aJapanese ophthalmologist (see below).9 The visual fielddefects among soldiers studied by Holmes included homony-mous hemianopia, quadrantanopia, paracentral scotomata,and extensive loss of peripheral vision. These visual fielddefects could not account for all the soldiers complaints,however, because they failed to notice or attend to images thatfell on retinal regions where sensibility was intact or onlyslightly affected.2 Holmes distinguished this problem fromthe unilateral disturbance of visual attention that can accom-pany parietal and lateral occipital lesions (the hemineglect inBlints). The soldiers erred in counting coins (for example, bycounting the same coins twice) and had trouble navigating(that contrasted unfavourably with a blind man) andreaching toward targets within central or peripheral vision.Holmes attributed these difficulties to a combination ofdefects: the spatial localisation defect, failure to attend toobjects in the periphery, and defective fixation and search. Heand Horrax attributed the brain damaged soldiers impair-ments in looking for and counting objects, reaching, reading,and writing to constriction of visual attention to one object(simultaneous agnosia) plus spatial disorientation.10 Holmesthought that his soldiers inability to touch with the handobjects located in central or peripheral fields was visionrelated, whereas Blint thought that the limb control defect hefound was somewhat independent of a visual deficit.

Holmes estimated the survivors brain lesions by assuminga straight course of a single missile between the entry and exitwounds in the skull. All apparently had bilateral lesions of thevisual cortex in dorsal and lateral locations. A postmortem ofsoldier 5 showed an entry wound in the left hemisphere,destroying the supramarginal gyrus with exit from the rightangular gyrus. Soldier 2 had an entry wound in the right lat-eral occipital lobe with exit from the left angular gyrus.Holmes thought that damage to the angular gyri and theirconnections could affect spatial orientation yet leave visualperception intact, and could disturb the centres from whichthe eye movements are elicited, with consequences for ocularfixation, accommodation for near objects, and blinking. Hefavoured Starlings idea that these areas performed anintegrative function for visual impressions from the retinaand tactile and muscular sensations from all parts of thebody.2 10

Holmes later explained that localisation in space by visionis not a simple perception or an innate faculty, but isacquired in childhood by correlating and integrating other

sense impressions with visual perceptions and depends onintegrity of anatomical paths linking visual perception withmuscular and tactile impressions from all parts of the body,including the ocular musculature. He reasserted that promi-nent disturbances of visual orientation result from bilaterallesions of the parieto-occipital regions of the brain, and espe-cially from those which involve the subcortical white matter inthe neighbourhood of the angular gyri, but defective localisa-tion in homonymous halves of the visual fields may be causedby injury of this portion of the opposite hemisphere.8

Hcaen and Ajuriaguerra coined the term Blints syn-drome in a 1954 report on four patients who exhibited slug-gish exploration of their visual environment.11 The sluggish-ness was attributed to sticky fixation (restriction of fixationto a single point) and emergence of a primitive grasp reflexaffecting the eyes. They also commented on a motor controldefect due to possible damage in the posterior parietal andoccipital association areas concerned with ocular pursuit.These patients had extensive brain damage, however, withimpairments ranging from extensive visual loss to stupor, andtherefore yielded few data to test the authors ideas.

Luria reported on a Polish officer who was shot in the headduring the second world war.12 The brain damage led to dis-orders of simultaneous perception, vestibular giddiness, andfits. Although the officer was adequately able to perceiveobjects, he exhibited severe constriction of the visual fieldsduring a perimetric examination and moved his eyes betweenobjects in a confused and inadequate manner, causing fail-ure to fixate one or more of the objects present. Like Blintspatient, the officer neglected objects on the left, showed defec-tive hand movements under visual guidance, and showedsimilar helplessness of gaze.13 Luria suggested a limitationof visual attention, incapacity to combine details into acoherent whole, and piecemeal perception due to weak-ness in cortical tonus that caused each focus of excitationin the visual cortex to inhibit the remainder of the visual cor-tex by negative induction. In a famous illustration, Tylerdepicted the limited ocular scan paths in a patient withBlints syndrome.14

Evidence suggests that Tatsuji Inouye, a Japanese ophthal-mologist, made independent scientific observations thatresemble and even antedate the findings in Blints initialreport (in 1907 in Hungarian15). Inouye studied Japanese sol-diers who were shot in the head during the Boxer Rebellion of1900 and the Russo-Japanese war of 19045.9 (His conclu-sions, originally written in German, were recently made avail-able in English.16) Inouye applied perimetry testing and useda craniocordinometer to estimate brain lesions from entryand exit wounds in survivors. He was familiar with the workof Henschen17 and von Monakow18 on localisation of visualfunction, and proposed a modern, anatomically accurate mapof the primary retinotopic representation in the calcarine cor-tex (striate cortex or area V1) before Holmes and Lister.19 Hespoke against war and advocated for soldiers pensions basedon quantitative test scores and functional outcomes.

Several of Inouyes patients (cases 511) had inferior hemi-anopia, a loss of vision in one or both of the lower visual fields,

Figure 1 Blint depicted the lesions in his patient in schematic diagrams showing the lateral surface of the hemispheres.

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compatible with the lesions of the dorsal (parietal) visualpathways typically reported in cases such as Blints.Sub-lieutenant Nobuta (case 6) was wounded on 14 July 1900in Tsien-Tsien. Perimetry (on days 55 and 824) showed bilat-eral inferior quadrantanopia that spared the macula. By day 61Nobuta could avoid obstacles and by day 108 he could readindividual letters, yet these did not form a unified sentence.Inouye noted a right occipitoparietal entry wound and leftexternal occipital protuberance exit wound and marked dam-age in the cuneus (the dorsal visual area bounded by the cal-carine and parieto-occipital fissures).

Infantryman Nambu (case 7), 26 years old, was shot in theocciput with a small calibre bullet while kneeling andshooting on 18 July 1904 at Port Arthur. He seemed confusedand totally blind. He could not see in his lower visual fields andhad a scotoma in the central 4 degrees of each upper field.Later, his sensorium was clear, visual acuity was 2/60, pupils,lids, and extraocular muscles worked normally, and he had noalexia, agraphia, or psychic blindness (associative agnosia,Lissauer type20). However, he moved only with help fromsomeone else and acted and walked as if he were blind (days294 and 476), resembling Holmes description. The wound wasexplored with temporal lobe resection. Inouye indicated thatthe patient had lesions of the cuneus that extended deep intothe substance of the occipital pole.

Infantryman J Arai, a 25 year old (case 26), had a smallcalibre bullet wound to the caudal right parietal region, withexit from a symmetric location on the left. On day 75, visualacuity tested with a chart using forms was almost normal, butthe doctor had to point to individual elements on the chart,otherwise Arai mixed them up. There was no associativeagnosia. On day 166, while walking, Arai would sometimesbump into objects that he could apparently see (much asinfantryman Nambu and Holmes soldiers). For safetys sakeArai walked in a crab-like fashion. To fixate objectspositioned above, below, left or right, he had to move his facein that direction, suggestive of ocular apraxia. Signs of speechdisturbance were present. Visual fields showed strong concen-tric narrowing through day 204, but colour perception seemedto be normal. Inouye reasoned that the principal lesionaffected the left angular gyrus and spared the optic radiations.

By contrast, Private Takeda (case 2) was shot in the leftocciput and found lying in a bank of snow at Sha-ho on Janu-ary 28, 1905, but did not show visual attentional or visual spa-tial disturbances as in the above soldiers or Blints case.Takeda had a right homonymous hemianopia that sparedfixation, associative agnosia, and optic aphasia (pure alexia).He also called red green and green blue, despite the excellentlighting conditions (clear weather) under which the colourtargets were presented. Inouye interpreted this as weakness ofcolour memory, although cerebral achromatopsia or colouranomia would be just as likely. Generally, lesions of the ventralvisual association areas (along the occipitotemporal or whatpathway), as in Takeda, tend to produce defects such as purealexia, associative agnosia (including prosopagnosia) andachromatopsia. This differs from the pattern of defects thatfollow dorsal (superior occipital and parietal) lesions reportedin cases of Blints syndrome.

ROLE OF CASE REPORTSHistorically, Blints syndrome has been based on single casestudies. This could be because the syndrome is relativelyuncommon; also, the bilateral lesions in these cases causeextensive visual, sensory, and cognitive impairments thathinder testing. Although single cases have provided valuableinsights into the anatomical substrates of vision, attention,and visuomotor control, the variability of lesion effects hasbeen underappreciated. Interesting abnormalities are likely tobe reported, and less striking cases are likely to be ignored,creating a biased picture concerning lesion effects. Lesion

effects and degree of recovery vary for broad reasons such aspatient age, time since lesion onset, and amount of whitematter involvement. Also, not all patients with similar brainlesions show the same deficits. Some patients were studied inthe acute phase of injury, at the zenith of behavioural deficits,whereas others were studied in the chronic phase of recovery,months or years later. A review of two dozen reports ofsimultanagnosia/Blints syndrome covering the 9 decadesafter Blints initial work showed a diversity of behaviouraldeficits, brain lesions, vision assessment techniques, opera-tional definition of terms, and opinions on underlyingmechanisms.21 The diverse aetiologies include cerebrovasculardisease, as in Blints original case (especially watershedinfarctions),22 tumour, trauma, prion disorders such asCreutzfeldt-Jakob disease, and viral infections such as HIV.Neurodegenerative conditions such as Alzheimers disease23 24

might be the most common cause of Blints syndrome.Scientific concerns surround key cases upon which Blints

syndrome is grounded, due to failure to assess basic visualfunctions (other than acuity and, occasionally, stereopsis), andto consider confounding eye conditions (such as retinopathy,cataracts, or optic neuropathy). In this vein, Blint1 claimedthat his patient had normal visual fields but it is unclear whichprocedures support this conclusion in a man who was likelydifficult to test. It is risky to generalise from historical or mod-ern single case reports in Blints syndrome.

SIMULTANAGNOSIA VERSUS VISUALDISORIENTATIONKey case studies on which Blints syndrome is based haveproposed differing mechanisms to account for the perceptualunderpinnings of the disorder. Blint suggested that hispatients main problem was a spatial disorder of attention.This occurred in the context of a left visual hemineglect syn-drome. Blint inferred that his patient could see only oneobject at a time no matter what size, a condition later calledsimultanagnosia.12 Yet, Blints findings indicate that hispatient could actually process multiple stimuli in somecircumstances (for example, while navigating).25 Also, objectrecognition can proceed economically from just a few key fea-tures, and identifying a person or object is not the same asseeing him, her, or it all at once. Along these lines, Holmesexplained that recognition does not depend on synthesis ofall the sense impressions derived from an object, the object isusually recognised as a whole, not as the sum of its parts andit is not necessary that the mental image should correspondexactly with the perception of the new object, or contain rep-resentations of all its features; images stored in memory areparticulate, that is, they consist of a number of parts each ofwhich represents a feature of the object remembered.8

Simultanagnosia should not be confused with agnosia, anassociative (or mnestic) disorder, in which percepts arestripped of their meanings.26 In Holmes words, agnosia isthe inability to recognise objects perceived by one of thesenses that occurs when sense impressions are unimpairedand mental images are intact.8 Patients with agnosia can nolonger recognise previously familiar objects or learn newobjects; in a restrictive form, prosopagnosia, the defect is mostapparent for faces.22 Patients with Blints syndrome maynot recognise objects due to their perceptual impairments, asdescribed under Lissauers old term apperceptive agnosia.19

In reality, most people with visual object recognition defectsprobably have a combination of associative and perceptualdeficits.

Wolperts definition of simultanagnosia can be operational-ised as an inability to report all the items and relations in acomplex visual display, despite unrestricted head and eyemovements. A suitable screening tool is a picture containing abalance of information among the four quadrants, such as theCookie Theft picture.27 The patients report can be correlated

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with a checklist of the items in the picture. Exclusion criteriashould include aphasia severe enough to impair the verbaldescriptions of a display, to avoid confusing a defect oflanguage with one of visual perception. It is also crucial to beaware of defective visual acuity or fields. Extensive visual fieldloss caused by double homonymous hemianopia (or keyholevision) (see the case of Luria12), or a central or paracentralscotoma, may hinder simultaneous perception and visualsearch, and objects may even seem to vanish.28 Rafalcommented that Wolperts definition of simultanagnosia isspecific to figure drawings but is more general than theconstriction of attention seen in Blints syndrome.29 On theother hand, simultanagnosia has been reported with bilaterallesions of the superior (dorsal) portions of both occipital lobesin Brodmanns areas 18 and 1928 in patients who do not displaythe full picture of Blints syndrome seen after lesions ofparieto-occipital areas and angular gyrus,29 suggesting thatsimultanagnosia may arise from damage to different areas ofan interconnected network of areas responsible for perceptionand attention (fig 2).

Holmes2 and Holmes and Horrax10 distinguished betweenvisual disorientation and the unilateral defect of visual atten-tion and the defect of simultaneous perception emphasised byBlint. Visual disorientation was due to errors in judging thelocation and distance of an object, and in judging the relativedistance between two objects. Although Blints syndromedepends on both visual spatial disorientation defects and theconstriction of attention,29 the inability to see more than oneobject at a time due to simultanagnosia seems to be sufficientto account for difficulty judging the distance between twoobjects, a crux of visual spatial disorientation.2 10

As we shall see, visual disorientation (as in Holmessoldiers) and simultanagnosia (in cases such as Blints)might each be generated out of differing combinations from

the same large menu of defects. This includes low level spatialresolution problems (affecting visual acuity and contrast sen-sitivity), visual field defects (such as tunnel vision andparacentral or central scotomata); motion processing deficits(cerebral akinetopsia), impaired ocular pursuit of moving tar-gets, and impairments of visual attention and visual workingmemory. There are multiple cues to structure and depth thatcould be affected by brain lesions that cause Blintssyndrome, yet the role of these potential defects in thegeneration of Blints syndrome is virtually untested.

SYNDROME STATUSBlints syndrome may not exist as a sufficiently autonomouscomplex to satisfy Bentons criteria30 for a syndrome.25 Firstly,the individual components of Blints syndrome are not asclosely bound as might be expected. For example, simultanag-nosia is doubly dissociable from optic ataxia.22 Ocular apraxiadoes not occur independently of visuospatial defects, but isitself often absent. Secondly, the individual components ofBlints syndrome (such as simultanagnosia and optic ataxia)seem to represent relatively broad categories comprising othermore specific defects. Thirdly, patients often have confoundingbehavioural defects, as in the cases of Hcaen andAjuriaguerra.11 Finally, the terminology and related opera-tional definitions of syndrome components vary acrossstudies.

Blints syndrome has been construed as a biparietalsyndrome,29 31 yet does not seem to have the specificneuroanatomical significance (of damage in the angular gyri)originally attached to it and may occur with other combina-tions of lesions. Consider a lesion of the left lateral geniculatebody or optic radiation causing right homonymous hemiano-pia, followed by a lesion in the right parietal lobe producingleft hemineglect. Vision might be restricted to the neglected

Figure 2 Transverse CT images of the brain in a patient with simultanagnosia show bilateral lesions restricted to the superior visualassociation cortex of the occipital lobes (visible as dark or wedge shaped areas located at the bottom portion of each image).28

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field and the patient would seem to have Blints syndrome(see the comparison below with hemineglect syndrome). Also,it is not clear that the components of Blints syndrome haveany special status compared with other defects associatedwith lesions in a similar location. Lesions of the right angulargyrus often correlate with hemineglect, and lesions of the leftwith aphasia and Gerstmanns syndrome (agraphia, acalculia,and right/left disorientation).30 Bilateral lesions around theangular gyri have been associated with a profound defect ofvisual motion processing,32 a defect not emphasised by Blint.

Holmes recognised that visual disorientation was stronglyassociated with multiple behavioural deficits:

As a result of visual disorientation, a patient may beable to find his way about even in familiar surroundings,and owing to the failure to recognise the positions anddistances of objects, he may collide with obstacles, andmay even walk into a wall although he sees it directly. Heis also unable to grasp or point accurately to objectswithin the range of his vision . . .Topographical memoryis often disturbed, too; the patient is then unable to visu-alise or describe routes with which he is familiar, as howto go from one room to another of his house, or from hishome to a neighbouring shop or station. Occasionallythe distinction of right and left of his own body or ofspaces is lost; this may complicate acts in which visualguidance is required . . .Visual memory, or ability tovisualise familiar persons or objects, may also be defec-tive . . .Visual agnosia is often combined with spatialdisorientation or spatial agnosia, or with defects of topo-graphical memory or imagery, and sometimes withinability to describe familiar objects which are knownchiefly by their visual.8

Blints syndrome may occur with bifrontal lesions33 and,perhaps, with pulvinar lesions.34 Lesions of Brodmanns areas6 and 8 (the frontal eye fields) may hinder voluntary saccades,visual search, and scanning, compatible with ocular apraxia.Elements of optic ataxia are associated with a wide variety oflesions in Brodmanns areas 5, 7, 19, 39, 37, and a profoundreaching disturbance has even been reported with a relativelymesial right temporo-occipital lesion.35 Optic ataxia may com-prise a family of defects. Inability to reach and grasp targets inthese cases is often multifactorial, including V1-type visualfield defect, defective visual attention, and inability to locatetargets with the eyes. Another possibility (described furtherbelow) is abnormal sensorimotor transformations, an inabilityto transform the visual coordinates of external objects toappropriate limb coordinates for generating accuratereaches36 (see the section below: Visually guided reachingand optic ataxia).

DORSAL SIMULTANAGNOSIA VERSUS VENTRALSIMULTANAGNOSIAThe primate visual system is partly understood in terms ofparallel pathways beginning in the retina. The parvocellular orP pathway, named for its connections to the simian striatecortex (area V1) via parvocellular layers 3 to 6 of the lateralgeniculate body, is characterised by colour opponency andslow conducting axons that convey sustained signals.37 38 Thisventral or temporal (what) pathway has strong projec-tions to secondary areas such as V4, V8, and IT (inferotempo-ral area), located in the inferior occipital lobe and adjacentoccipitotemporal regions.39 Damage in these regions mayimpair pattern recognition and learning, producing agnosiafor objects and faces (prosopagnosia) and inability to readdespite prior literacy (alexia). Also, damage to these areas canreduce colour perception in the contralateral field, a condition

known as cerebral achromatopsia (see Inouyes descriptionabove of private Takeda 16).40 41

By contrast, the magnocellular or M pathway is comprisedof large diameter, fast conducting axons that conveyinformation about transient visual signals, connects via V1 tosecondary visual areas including area V5 (mediotemporalarea) lying along the dorsal or parietal cortical (where)pathway, and is thought to support motion perception. Dam-age in these areas produces disorders of spatial-temporalanalysis (the inability to judge object location, distance, orien-tation, size, or motion) as well as marked disturbances ofvisually guided eye and hand control. The hemineglectsyndrome and Blints syndrome are remarkable examples.29

Against this backdrop, it has been suggested that patientswith Blints syndrome have dorsal simultanagnosia withattentional limitations that preclude the detection of multipleobjects, whereas patients with ventral simultanagnosia haveleft occipitotemporal lesions with slowed visual processingspeed, causing a difficulty in simultaneously recognising theindividual parts of a multipart object, with manifestationssuch as letter by letter reading.4244 Proposing different forms ofsimultanagnosia reinforces the myriad behavioural differ-ences between patients with dorsal and ventral systemlesions, which have been well described (as in the literature onacquired alexia in patients with left occipitotemporal le-sions45). Although patients with ventral lesions and those withdorsal lesions may both seem to have simultanagnosia, theunderlying causes of the simultanagnosia are differentdepending on the location of the lesion (dorsal versus ventral).Further research is necessary, however, on these twocategories of simultanagnosia.25 The dorsal and ventralsystems might conceivably share similar processing mecha-nisms, which could allow a dorsally damaged patient topresent with behavioural impairments characteristic ofventral damage. For example, slowed processing of letter pat-terns can occur with lesions in dorsal areas such as the angu-lar gyrus and might make such a patient seem to read in a let-ter by letter manner. Thus, generalised slowing can be causedby lesions in either dorsal or ventral visual areas and can helpto explain information processing impairments and perform-ance loss at multiple levels46 on cognitive tasks ranging fromsimple memory to complex reasoning and spatial abilities.46 47

This includes reduction of the useful field of view, a constric-tion of the visual fields in the absence of visual sensory loss onstandard perimetry testing.48 49

Of note, visual mechanisms for object recognition andlocalisation seem to depend on processing of signals in struc-tures that are outside the visual cortices proper, such as thefrontal lobe50 51 and cerebellum.5255 We should consider thepotential importance of lesions in these areas to form a morecomplete picture of Blints syndrome. The prefrontal cortexalso seems to be a destination of visual signal processing thatbegins in the primary visual cortex and plays a part in visualattention by altering the bias among competing signals in theextrastriate cortex arising from different parts of the visualfield.51 Ventral pathways for object vision seem to connect withventrolateral prefrontal areas involved in working memory forobjects, whereas dorsal pathways involved in visuospatialprocessing connect with dorsolateral prefrontal areas involvedmainly in working memory for spatial locations. The prefron-tal cortex also seems to support mechanisms for visual work-ing memory, the process of maintaining a representation ofinformation for a brief period of time so that it is available foruse.50 Impairments of working memory for objects and theirlocations could potentially contribute to perceptual manifesta-tions reported in Blints syndrome.

Patients who meet operational criteria for Blints syn-drome can also have damage to several of these mechanismsfor visual working memory, as in the case of Blints patient,and the well studied modern day case of patient RM.31 RMslesions occupied the parieto-occipital areas and white matter

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about the angular gyrus and posterior superior temporal lobe(see Friedman-Hill et al,31 their figure 1), but also affected theleft supplementary motor area and both cerebellar hemi-spheres. The cerebellum, with its multiple visual and motorconnections,53 54 may support neural mechanisms that distin-guish between image movement across the retina and selfmovement, and may contribute to perception of form fromtemporal structure alone (with the transient system carryingthe signal via dorsal visual pathways).56

ROLE OF ATTENTION AND WORKING MEMORYVisual cues convey a wealth of information about physicalobjects and their relations. Conscious appreciation of thisinformation is therefore likely to require focused attention.Many images compete for our attention, yet we cannot appre-ciate more than a few items at once. We experience items thatwe attend to for whatever specific purposes we have in mind,and we fail to perceive the rest.57 58 Without focused attention,the obvious may be hard to see: we can be oblivious to markedchanges in scenery (change blindness), and traces of retinalimages in visual short term memory (visual working memory)will fade without being consciously perceived or remembered(inattentional amnesia).59 The very act of perceiving oneitem in a rapid series of images momentarily inhibits the abil-ity to perceive another image (the attentional blink). Inshort, we seem to construct our reality from a sequence ofglimpses, and our impression of a seamless and richly detailedvisual world is something of an illusion.57 Damage to visualcortex and connections can destroy this illusion, resulting in apiecemeal experience in which the visual world seems to beconstricted to an erratic focus containing a single object at atime, as in the symptom complex described by Blint.1

Evidence from patients who display elements of thissyndrome is relevant to the understanding of the neural sub-strates of visual perception, motor control, short term (work-ing) memory, attention, and even consciousness.

Blints report provided early information that the visualcortex and connections among visual areas play a crucial rolein visual attention. This role is carried out at several functionallevels and seems to depend on both dorsally and ventrallylocated visual cortices and their connections. Objects in thevisual field always compete for focal attention.6062 Althoughvisual attention may amplify extrastriate neuronal responsesto a stimulus at one spatial location in the visual field, record-ings in the extrastriate cortex of monkeys suggest that sucheffects rely on competitive interactions among neurons repre-senting all stimuli in the visual field.51 Attention can be biasedtoward target stimuli by spatial and non-spatial processing aswell as bottom up and top down processing, suppressing neu-ronal representations of behaviourally irrelevant stimuli in theextrastriate cortex.51 63 Top down influences may derive princi-pally from neuronal systems for working memory.51 Patientswith Blints syndrome might fail at both top down and bot-tom up levels, as suggested by PET studies of visuospatialattention.64 The inability to perceive more than one object at atime in Blints syndrome suggests the importance of aparietal based spatial attention network in recognising multi-ple objects, consistent with computational models of attentionand recognition.65 66

Activation of frontal areas during interactions betweenvisual processing, working memory, and sustained attention,derive from PET, fMRI, magnetoncephalography, and eventrelated potential research.67 The prefrontal cortex is involvedin behavioural tasks that require decisions based on workingmemory, and visually related areas of the prefrontal cortexwould represent the final point in a proposed hierarchicalsequence of visual signal processing that begins in the primaryvisual cortex.68 Ventral pathways for object vision seem to con-nect with ventrolateral prefrontal areas involved in workingmemory for objects. Dorsal pathways involved in visuospatial

processing and generally implicated in Blints syndromeseem to connect with dorsolateral prefrontal areas involvedmainly in working memory for spatial locations.50 Recognitionof a specific visual target among equally familiar distracters isassociated with both an enhanced response to that target inthe frontal cortex that persists with target repetition, and areduced response in the extrastriate visual cortex with stimu-lus (target or distracter) repetition, a process that may fail inthe case of Blints syndrome.69 These complementary neuralmechanisms track the status of familiar items in visual work-ing memory, allowing efficient recognition of a relevant objectand rejection of irrelevant distracters.70 Failure of thesemechanisms in neurological conditions such as Blintssyndrome can provide information about how (1) spatialattention provides the glue that allows elementary featuressuch as colour, shape, or size belonging to a stimulus to begrouped (the binding problem); (2) image features such asline segments are grouped to form larger structures such assurfaces or regions; (3) object parts are encoded relative to areference point on the object itself (an object centeredrepresentation); and (4) focal visual attention interacts withvisual features such as colour and shape to guide visual targetsearch.71

In biased competition accounts of visual search,51 63 72

attentional selection is guided by: (1) bottom-up sources thatarise from perceptual processes and (2) top-down sources thatarise from goal directed, executive processes. Lesion studiesillustrate the role of the visual cortex in maintaining the per-ceptual processes that operate on the bottom up inputs in thebiased competition model and also are compatible with resultsin non-human primates, indicating the role of both V4 and V5(mediotemporal area) in bottom up attentional processing.For example, Schiller73 maintains that simian V4 is part of aneural circuitry that contributes to the selection of crucial,physically less prominent stimuli, which in early parts of thevisual system evoke less activity than other stimuli in thevisual scene. In addition, the receptive fields of neurons in V4and IT are suppressed when attention is directed to one of twotargets, as if the receptive fields were shrinking around theattended location.74 This resembles shrinkage in the usefulfield of view measured by patients with Blints syndrome andwith lesions of the early visual cortex.75 Shrinkage of the use-ful field of view due to reduced processing speed and attentionrather than hemianopia has since been identified as a conse-quence of aging48 49 and age related neurologicalimpairments.75 76

The visual fields in Blints patient were easily fatiguable,resembling the effects of fatigue in normal observers (such asair traffic controllers) with prolonged and intensive monitor-ing of visual displays.77 78 Holmes noted such effects inmeasuring the fields of vision in the clinic and wrote: Even innormal persons the field becomes smaller and the reply is lessaccurate as the subject tires; it is therefore often advisable tointerrupt the examination for a time, or rest the subject, ifthere is any sign that his attention is flagging.8 The effects inBlints patient, however, were pathological and did notrequire prolonged effort. Still, Blints patient could immedi-ately and always see targets in his neglected left hemifieldwith the aid of verbal prompts, suggesting that Blints patientcould disengage attention from the right visual field, shiftit to the left, and engage targets there like normalsubjects79 80 and some modern lesion cases.81 82 In other cases,however, disengagement of attention may be abnormal, andocular apraxia and simultanagnosia might even be explainedby an inability to disengage attention from fixated objects,42 83

reminiscent of the visual grasp reflex hypothesised by Hcaenand Ajuriaguerra in their cases.11 Patients may have to closetheir eyes to break fixation from one object so they can look atanother. If attention is needed for conscious perception ofobjects, restriction of attention to the fixated object might helpexplain simultanagnosia.

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Blints syndrome might also reflect loss of a master spatialmap within a feature integration framework.84 In this frame-work, attention operates beneath conscious awareness,helping the mind to group different features and attributes ofobjects. Patients with cerebral lesions may be unable to iden-tify which features in the panorama (for example, colour andshape) belong to an object and may therefore form illusoryconjunctions.31 For example, when presented with a rapidpresentation containing a red O and a green X, the patientmight erroneously perceive a green O and a red X. In asimilar vein,29 when patients with Blints syndrome viewoverlapping figures (such as a comb and a spoon), they see oneor the other, but not both; alternatively, they may see neitherand therefore generate an incorrect answer by focusing onlocal elements in the display (analogous to the parable of theblind man and the elephant).

Patients with Blints syndrome may have difficulty switch-ing attention between local details and global structurethatis, they cannot see the forest for the trees. This type of deficitcan be investigated using hierarchical stimuli such as a largeglobal letter made of smaller local letters (for instance, alarge letter C made of multiple smaller versions of the letters). Neural mechanisms of global/local attention may differfrom mechanisms for object/part attention. Attention toobjects and parts can be tested using objects having threeparts: a vertical body and two crossbars (fig 3).85 There are twofeatures (small bumps) at the end of the crossbars. Thesebumps can be on the same crossbar or on different crossbars.Subjects are asked to compare the bumps and report if theyare identical or different. Normally subjects are better able tocompare features that are on the same part (the samecrossbar) than those on different parts (different crossbars),but these results may vary in patients with neurologicalimpairment such as Blints syndrome. If part attention andspatial attention are controlled by separate neural processes,patients with ventral pathway damage should not show partattention effects (better performance in the same-part condi-tion than in the different-part condition), but should showintact spatial attention (better performance when bumps arenear one another regardless of the part they are on). It is pos-sible that subjects with damage to the dorsal visual pathway(as in hemineglect) might show the opposite pattern; that is,intact part attention but disrupted spatial attention. Forexample, in hemineglect, a part that crosses the visual midlinemay reduce hemispatial neglect or extinction, consistent withsome reports of object centred neglect.86 Further, patientswith Blints syndrome might exhibit a simultanagnosia formultipart objects, failing to appreciate all of the parts simulta-neously and only reporting one of the parts.

Experiments using the Sternberg paradigm87 can revealconnections between basic visual processing, memory, andattention in patients with cerebral disorders of vision such asBlints syndrome.88 Subjects view a series of stimuli (complexpatterns that resist verbal encoding) and judge whether asubsequent probe stimulus was part of the series. Performancevaries with series length and position of the probe in theseries, more recent positions allowing better recognition.When the stimulus series contains a single item, the procedurecomprises a simple visual discrimination paradigm, but withadditional items in the series, it constitutes a recognitionparadigm. Varying the dimensions of stimulus similarity per-mits quantitative assay of recognition memorys potentialstimulus related and task dependent antagonists, includingboth visual and memory factors. Visual recognition memoryuses different neural pathways, depending on stimulusattributes, task demands, and behavioural goals.89 Thismemory is robust over short time periods for basic attributessuch as spatial frequency, orientation, and motion direction,90

allowing normal subjects to compare and make inferencesfrom relations between different items in the environment,but declining rapidly with interference from successive inputs.

Sternbergs recognition memory procedure87 can be used toexamine the effects of such interference on the visualsystem.88 Results in normal subjects show that series lengtheffects in recognition memory reflect both the number ofintervening items and the length of the number of items in theseries. Recognition is unaffected by delays of up to 4 seconds.Time alone is not a major source of forgetting with shortintervals, even with complex stimuli. However, performancemay decline with lesions in visual pathways, or with deficits ofvisual working memory that depend on prefrontal cortex.50

Alzheimers disease affects vision91 92 and visual attention76 andmay cause Blints syndrome. Pilot studies in our laboratory infour persons with Alzheimers disease, conducted in collabora-tion with Dr Robert Sekuler, showed that the results withseries length (n=2) may help distinguish between impair-ments of early vision and visual working memory and atten-tion.

What are anatomical substrates of the attentional mecha-nisms that may be impaired in Blints syndrome? Currentevidence suggests the following hypotheses:

(1) Visuospatial attention and temporal attention dependon a network of structures that includes occipital areas 17, 18,and 19 (both dorsal and ventral), connections with temporaland parietal lobe regions (especially the inferior parietallobule on the right), frontal eye fields, and prefrontal cortices.

(2) The ventral pathway is crucial for bottom up object rep-resentation and memory.

(3) The ability to perceive objects in rapid serial visual pres-entations depends on dorsal (psychophysical transient) path-ways and their parietal connections.

Figure 3 Examples of stimuli used to study part based attentionalselection.71 Observers are asked to judge if the critical features (thebumps) of an object look the same or different. The bumps canappear on either the same part or on different parts, but are alwayslocated the same spatial distance from one another. Neurologicallyintact observers are faster to discriminate critical features that arelocated on the same part of an object.

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(4) Executive switching of attention between visual objectsand tasks depends on areas in the prefrontal cortex that influ-ence the dorsal and ventral visual pathways in a top downmanner.

Blints syndrome and the hemineglect syndrome probablyaffect several of these hypothetical mechanisms, includingspatial attention, the enhancement of object representations,and the encoding of objects into visual working memory.

RELATION BETWEEN BLINTS SYNDROME ANDTHE HEMINEGLECT SYNDROMEElements of the hemineglect syndrome, a disorder of attentionin which patients with right hemispheric lesions (usually) failto register targets in the opposite panorama, feature promi-nently in reports by Blint and other influential researchers; adiagnosis of hemineglect has never excluded a diagnosis ofBlints syndrome. It is possible that Blints syndrome is dis-tinct from hemineglect syndrome because the critical lesionsin Blints syndrome are bilateral and occupy the parieto-occipital junction, whereas lesions in the hemineglectsyndrome occupy the temporoparietal junction and typicallyaffect the angular gyrus.29 Yet these anatomical distinctions arenot clear cut, and the behavioural overlap between these twosyndromes is obvious.

Patients with hemineglect syndrome may have defectivevisual search (using eye movements93 that resemble ocularapraxia) and defective hand movements under visual guid-ance (with both hands into the neglected hemifield and withthe limb on the neglected hemibody to all fields) that resem-ble the pattern of optic ataxia.94 95 Patients with hemineglecthave visuoperceptive disturbances that resemble simultanag-nosia, including extinction of objects in the bad hemifieldwhen stimuli are present in both fields, or even when multiplestimuli are simultaneously displayed in the good field alone.

Blints patient had left hemineglect due to extensive dam-age in the right inferior and superior parietal lobules. Lesionsin these locations are likely to produce visuomotor difficulty inreaches conducted with the left hand to both visual fields(hand effects) and with both hands to the left visual fields(field effects).96 97 Blint emphasised that his patient hadtrouble locating visual targets with the right hand, but lefthand control could also have been impaired. Observations onthe reaching behaviour in patients with focal circumscribedlesions of visual cortex can help clarify these issues.

Holmes8 commented on attention hemianopia affectingone or both hemifields. He wrote that when a subjects atten-tion is poor, or when it tires, his replies to stimuli, especiallythose falling in the periphery or less sensitive portions of theretina, tend to be inaccurate and unreliable. Under these con-ditions, the visual fields, particularly when mapped up by aperimeter, become gradually smaller and the contours irregu-lar, this is frequently so in hysteria and in cases of exhaustion.He also noted that a specific local loss of visual attention inthe hemianopic halves of the visual fields, or in some portionsof them, may, however, result from cerebral lesions involvingthe opposite parieto-occipital lobe. When it is present the fieldmay be normal and isolated stimuli perceived with accuracy,but no reponse may be obtained, or only a proportion of thestimuli are perceived, on the affected side which attention isdiverted or claimed by another stimulus. This can be demon-strated by the observer holding up his two hands, one on eachside of the fixation point and at roughly equal angles from it,and requesting the patient to reply to every movement of afinger or thumb. Regular responses are obtained if a finger oneither side only is moved, but on simultaneous movements ofthe fingers to both the right and left, that on the affected sideis not perceived or a proportion of them only may be noticed.The intensity of the stimulus to the affected side has littleinfluence on this phenomenon; it may, for instance, bedemonstrated by using a test object one centimeter in

diameter on the normal side and one of 20 centimeters on theother. He further states that when vision is reduced in thehomonymous halves of the field the responses to small objectsmay be irregular and inconstant; it is therefore necessary toexclude visual defects and use large stimuli in testing forvisual inattention.8

Riddoch reported that spatial disorientation may occur inhomonymous half fields alone.98 He studied two patients whohad unmistakable visual disorientation in the right ho-monymous hemifields. Both patients were unaware of thedefect, which persisted until death. Both died several monthsafter a neurosurgical procedure that showed a malignanttumour of the left parietal lobe. Visual acuity was reducedslightly to moderately. The first patient, a 58 year old retiredbusinessman, had enlargement of the blindspot in his left eye,probably due to increased intracranial pressure, but had nohemianopic defect. This patient could quickly fix his gaze onan object and maintain it to his left, but was less consistent tohis right, which resembles the defect in hemineglect. The sec-ond patient, a 34 year old farmer, had papilloedema and anincomplete right homonymous hemianopia with gross defectof localisation of objects and estimation of distance in his righthemifields. He usually pointed below and beyond objects.Visual attention was impaired in the right half fields.Although visual fields and attention improved after surgery,the patient still showed gross spatial disorientation, espe-cially for absolute distance. In his defective fields, however,he recognised, without hesitation, the shape of a cube, asphere, a pyramid, and a cylinder. Riddoch downplayed therole of a visual attention defect, in line with Holmes opinionthat it does not form an essential part of the syndrome of dis-ordered space perception. Riddoch concluded that (1) visualdisorientation can result in the fields opposite a parietal lobelesion; (2) the defect can be dissociated from other relateddisorders of visual function that follow lesions in roughly thesame part of the brain; and (3) the defect is not due tohomonymous hemianopia or poor visual resolution. Hecautioned that because a patient could be unaware of thedeficiency, it may not give rise to obvious disability and musttherefore be sought by the examiner. He felt that he hadnothing to add to the views already expressed by Holmes onthe mechanism of the disturbance (visual disorientation)and agreed that so far as is at present known, the nodal pointseems to be in the region of the supramarginal and angulargyri in the parietal lobes.98

A neglected hemifield processes information much as asimultanagnosic field does. Patients with hemineglect syn-drome may have difficulty making feature conjunctions in theaberrant field and may make illusory conjunctions (forexample, of colours and letter shapes, as described above).99

Likewise, Blints syndrome patient RM reportedly miscom-bined colours and shapes, even under free viewing conditions,possibly due to an inadequate early spatial representation ormap of object features.31 Diminished ability to bind featuresfor unified perceptual objects represents yet another similaritybetween the hemineglect syndrome and Blints syndrome.RM reportedly had spatial disorientation, optic ataxia,psychic paralysis of gaze, hyperattention to a single object, anddifficulty reporting more than one object in natural scenes dueto embolic strokes affecting both parietal lobes. Like Holmespatients, RM could not judge accurately whether an object wasmoved toward or away from him. Visual acuity, spatialcontrast sensitivity, colour, and stereopsis were adequate.Goldmann fields showed an inferior nasal depression in theleft eye only, and there was no reported evidence ofhemineglect. It was not stated whether RM still metoperational criteria for Blints syndrome about 2 years aftersyndrome onset, when his ability to make feature conjunc-tions was tested. Patients with Blints syndrome, similarly tothose with hemineglect syndrome, can recover dramaticallyafter initial symptoms resolve.

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Visuoperceptual deficits in the hemineglect syndrome, as inBlints syndrome, are not limited to one hemifield. Onesource of supportive evidence comes from studies of theattentional blink, which refers to the inability to identifyobjects in the aftermath of visual recognition (fig 4).100102 Thisattentional blink normally lasts about 0.5 seconds and isthought to depend on the ability to allocate attention overtime and consolidate representations in visual workingmemory101 103; it may also involve scene representation,104 105

postperceptual processing,103 106 and magnocellular visualpathway function.107 Husain et al tested the attentional blink ineight subjects about 1 month after a right hemispheric strokeaffecting the inferior parietal lobe, inferior frontal lobe, orbasal ganglia.108 These patients had visual neglect definedclinically and on a shape cancellation task, but also had trou-ble perceiving foveal targets in a rapid serial visual presenta-tion task that used letter shapes as visual targets. They couldnot identify a second foveal target until 1440 ms had elapsedafter identifying the first target, indicating a pathologicallyincreased attentional blink. They concluded that visualneglect is an inability to direct attention in time, as well asspace.108 Increased attentional blink is not specific to thehemineglect syndrome109 and similar limitations may arise outof simultanagnosia or Blints syndrome,31 108 dementia,76 orcognitive aging.110 The increased AB that follows damage tothe dorsal pathway could be due to damage to an attentionalnetwork that does not direct attention in time itself, but ratherprovides input to a visual working memory system. Thedegraded inputs to visual working memory that arise from adamaged parietal based attention system could impair visualworking memory, leading to an increased attentional blink.

PERCEPTION OF STRUCTURE AND DEPTHTheories of visual perception include structuralism, gestaltism,and ecological optics, with varying emphases on nativism(vision is innate) versus empiricism (vision is acquired throughexperience), atomism (a visual field is the sum of its parts)versus holism (the appearance of one part is influenced by the

presence of others), organism (perception depends on struc-ture of the organism) versus environment (perception dependson external stimuli), and underlying principal analogy (forexample, to chemistry, physical field theory, or mechanicalresonance111). Yet another varying emphasis regards method ofresearch. For example, trained introspection versus naveintrospection (emphasised by structuralists) versus stimulusanalysis (emphasised in ecological optics by Gibson112 and laterby Marr 113). Blint primarily relied on a descriptive approachand introspective analyses. The approaches of Holmes andInouye were more in line with current strategies, which favoura combined cognitive neuroscience/visual psychophysicsapproach, with emphasis on optics and stimulus analysis.

The various perceptual phenomena reported in cases such asBlints patient (including vanishing objects, tilted vision,metamorphopsia, and palinopsia) are not likely to be thebehavioural expression of a single mechanism (such as theinability to see more than one object at a time25), but may bebetter explained as a variety of combined deficits from lesionsof the dorsolateral visual association cortices, which includesthe putative human mediotemporal area complex and its pro-jections to the parieto-occipital cortex. Damage to these areasand to the cortices surrounding the angular gyrus and parietalinsular cortex can disturb multiple aspects of attention, as wellas spatial and temporal processing, including the perception ofvisual motion,32 structure from motion and dynamic stereopsis,the perception of egomotion, and coordination of visual (eyecentred) and vestibular (gravity centred) coordinate systemsthat orient us in the physical world. Bilateral lower quadran-tanopias may co-occur (as in Inouyes and Holmes soldiers)from damage to the visual cortex along the dorsal banks of thecalcarine fissure, worsening a patients overall problem.

Impairments in the perception of objects and the relationbetween objects that contribute to Blints syndrome may berelated to lesions in neural structures that support perceptionof structure from motion and motion parallax and relatedprocesses. Holmes touched on these mechanisms when hecommented that localisation in the coronal plane depends

Figure 4 Schematic representation of stimuli used in a rapid serial visual presentation task (A and B) in studies of the attentional blink.109

W

A

X

A

B

Letter

White letter target

Black X

SOA

Time

Letter Target Blank BlankBlank Letter

SOA05 Between target letters

48 Pre target letters

Time

X

Whiteletter Black

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mainly on the local signs of the retinal point excited by theimage of the object, but the estimation of distance is a morecomplicated process which requires integrations of impres-sions of various origins, as those provided by binocular vision,proprioceptive impulses from the ocular muscles (especiallythose excited by convergence and accommodation), and judg-ments based on distinctness, light intensity, and the compara-tive size of familiar objects. Stereoscopic vision, which isrelated to the estimation of distance, may be affected at thesame time.8

Indeed, there are many cues to structure and depth thatcould be affected by brain lesions in Blints syndrome. Amongthese information sources on object structure and depth areaccommodation, convergence, binocular disparity, motionparallax, texture accretion/deletion, convergence of parallels,position relative to horizon, relative size, familiar size, texturegradients, edge interpretation, shading and shadows, andaerial perspective.113 These clues are optical (except accommo-dation and convergence, which are ocular), monocularlyavailable (except convergence and binocular disparity),stati-cally available (except motion parallax and texture accretion/deletion, which are dynamic) and relative (except accommo-dation, convergence, and familiar size, which are absolute).Most of these information sources are quantitative (excepttexture accretion/deletion, edge interpretation, shading andshadows, and aerial perspective, which are qualitative).111

PERCEPTION OF STRUCTURE FROM MOTIONPerception of structure from motion or kinetic depth is a longhypothesised real world use of motion perception111 114 thatmay fail in patients with lesions in the dorsolateral visual cor-tices. Structure from motion is efficient compared with othercues such as colour and luminance.115 Models of structurefrom motion extract discontinuity boundaries in a field oflocal motion vectors, with grouping based on common direc-tion or speed.116 Schiller73 found that mediotemporal arealesions, along with V4 lesions, produced some deficit in theperception of structure from motion. Marcar et al117 found thatmediotemporal area neurons in macaque responded to kineticboundaries, but that this processing was particular for thechange in local motion at the boundary and did not code theactual orientation of the boundary. Instead, neurons in theinferotemporal cortex show orientation selectivity for shapefrom motion as well as shape from luminance cues. Addition-ally, using functional imaging techniques, Orban et al118 founda right hemispheric area near but separate from the putativelocation of the human mediotemporal area homologue thatwas selectively active during a motion defined form task. Thelesions reported in cases of Blints syndrome often includethese areas.

For an objective test of structure from motion, we developeda two AFC shape identification task that asks a subject toreport the shape of the object presented in each trial (fig 5).Accurate performance depends on the subjects perception ofthe figures shape from motion. To prevent shape identificationfrom non-motion cues, such as edges or dot density, and toindex the difficulty of the task, varying amounts of randomdot noise are added to a background region surrounding thetarget. The perception of structure from motion was impairedin early Alzheimers disease70 and motion blind(akinetopsic)subject LM.32 LMs ability to perceive structure from motionbroke down at moderate levels of moving and stationarynoise.119 Aspects of LMs complaints, namely that she wouldsee objects in one place or another but not moving inbetween,32 are reminiscent of complaints in Blints syndrome.However, LMs complaints depended on moving stimuliwhereas the complaints of Blints patient did not. Relevant toinstrumental activities of daily life,structure from motiondeficits in subjects with brain lesions are associated with

increased relative risk for safety errors and car crashes in highfidelity driving simulation scenarios.120

DEPTH FROM MOTION PARALLAXPrevious studies have found that impairments of binoculardepth perception (stereopsis) are not sufficient to account forcritical features of Blints syndrome (for instance, troublejudging the relative depth of objects in space due to an inabil-ity to perceive more than one object at a time).10 29 However,other explanations may obtain, including lesions in a systemthat recovers information of object structure and depth frommotion parallax, stereopsis, and other cues.

Knowledge of structure and depth is critical for successfulinteraction with, acquisition of, and locomotion aroundobjects and obstacles in our environment. This information isso important that the human brain employs a redundant sys-tem of multiple visual depth cues including monocular andbinocular cues and relative movement. Yet monocular cues todepth (including familiarity, linear perceptive, and interposi-tion) can be deceiving, binocular depth perception (stereopsis)is not available to monocular subjects (or animals with later-ally placed eyes), and kinetic depth effect (or structure frommotion, see above) may provide ambiguous depth assign-ments. Motion parallax is one of the most important cues fordepth from motion121 and provides unambiguous informationon depth from information about direction of subject headmovement, and possibly slow eye movements.122

Binocular stereopsis and relative motion may assumegreater importance in conditions of high background noise orunfamiliarity. Disparate views from the two eyes generate dis-parity cues with an orderly geometric relation to relative dis-tance of objects,123 allowing the brain to recover depthinformation through a neural process resemblingtriangulation.124 Recovery of depth from relative motion relieson relative movements of retinal images. For motion parallax,relative movement of objects is produced by active movementof the subject, such as moving the head along the interauralaxis.125 For motion perspective, relative movement of objects isproduced by passive movement of the subject, as when thesubject looks out the side window of a moving vehicle.111 Inboth conditions, objects move in orderly relation to oneanother across the subjects retina, without changing theirlocation in the world. Objects further than the fixation pointseem to move in the same direction the subjects head is mov-ing, whereas closer objects seem to move in the oppositedirection. Relative velocities of these movements across theretina have an orderly relation to relative distances of objectsin the scene.111 126 127 Such orderly geometric relation make bothstereopsis and motion parallax unambiguous cues to relative

Figure 5 Kinetic depth perception stimulus. The left panel depicts arandom dot kinetic depth stimulus with a random dot noisebackground. Each dot would actually be moving. There is no obviousshape present in the two dimensional structure of the dots. The rightpanel depicts what is perceived by observers: a three dimensionalfigure (a cube depicted here) rotating about a vertical axis.

Schematic of stimulusviewed by observers

Schematic of figureobservers perceived

Rotationor

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depth. Unlike motion parallax, structure from motiongenerates ambiguous depth128 129 and can occur with a station-ary subject and relative movement of objects in ascene.128 130 131 Understanding the rules governing combinationof different depth cues (stereopsis, motional parallax, struc-ture from motion) into a single percept is an active researchtopic.132134 Feedback signals from slow eye movements mayalso be important.122 The cerebral lesions associated withBlints syndrome are likely to disturb this sytem at multiplelevels. Cerebellar lesions may also be implicated. The cerebel-lum plays a role in integration of head movement, eyemovement, vestibular and visual information, in the cortico-pontocerebellar system for slow eye movement control; and,possibly, in depth from motion parallax. Abnormal perceptionof depth from motion parallax could accompany smooth pur-suit eye moment deficits due to posterior (for example,parietal) hemispheric lesions135 136 or cerebellar lesions, both ofwhich were identified in Blints syndrome patient RF49 and inakinetopsia patient LM.119

MENTAL ROTATIONMental rotation represents a type of visual motion taskthought to rely on mental manipulation or movement of aninternal representation of a visual stimulus rather thanperception of visual movement and is likely to have beenimpaired in Blints patient. In a standard mental rotationtask,137 a subject presumably uses mental imagery to rotate avisual stimulus before it can be compared to a standard. Men-tal rotation may come into play in circumstances when wemust identify objects (or faces) encountered in non-canonicalorientations, and could place demands on the neural mecha-nisms for perception of motion. Although relations betweenreaction time and orientation of visual test figures have beendescribed,138 the underlying mechanisms are not well under-stood. Right parietal lesions139 (as in those in patients withhemineglect syndrome and Blints syndrome) producedlonger reaction times, more errors, and differential accuracyover the angle of rotation, compared with normal subjects andsubjects with left hemispheric lesions. A mental rotation taskmay increase activation in right parietal regions, but the leftinferior parietal lobes may also play a part.140 Brodmannsareas 39 and 19, thought to contain the human homologue ofthe mediotemporal area, was selectively activated in bothhemispheres in subjects performing a mental rotation task141

We used a version of a mental rotation task142 to testwhether selective damage to these areas would affect mentalrotation ability in a patient (SF) who had a limited resection ofthe anterior right occipital gyrus and the posterior sector ofboth the inferior and middle temporal gyri.143 This includesregions thought to correspond with primate area V5 (medio-temporal area) on the basis of functional imaging.144146 Fivedays after surgery, SFs mental rotation reaction timesincreased 380%, whereas reaction times on a control (lexicaldecision) task increased little. SFs mental rotation reactiontime function returned to normal by the 18th day, similar tothe transient deficits SF showed in tasks of movement percep-tion. The neural mechanisms for mental rotation and formovement perception seem to depend on a human homologueof area V5 (mediotemporal area), which can be affected insome patients with Blints syndrome

AWARENESS OF VISUAL IMPAIRMENTSHolmes noted that patients with suprageniculate lesions arefrequently unaware of loss of vision . . . and consequently maynot refer to it in describing their symptoms.8 He explained thatwe all have a body scheme that is built up of . . .visual, tactile,postural and other sensory impressions. When a part of thisscheme or image is injured the corresponding part of the bodypasses out of consciousness, and the patient is no longer awareof it and does not recognise any disturbance within it.8

Rarely, a patient seems to be completely blind due to a cer-ebral lesion yet denies the deficit, a situation described byAnton (1899)147 and later called Antons syndrome.148 149

Antons syndrome may share a common mechanism withother common forms of anosognosia, such as denial of lefthemiplegia or hemisensory loss in patients with a lefthemineglect syndrome after right hemispheric damage22

(which is relevant to Blints syndrome). Anosognosia hasbeen attributed to disconnection between the right parietallobe and thalamus150 and may reflect executive dysfunction inpatients with frontal lobe lesions.151

Patients who deny blindness generally have large lesionsthat extend beyond the occipital lobes in association withmultiple cognitive defects outside vision. A potential explana-tion for some cases of Antons syndrome is failure to conductan adequate examinationfor example, the patient hasresidual visual function and really is not blind, or has markedcognitive dysfunction that has not been documented.

Patients who have no experience of the items that theylocalise or detect in the fields of an area V1 (striate cortex)lesion have been described under the oxymoronblindsight.152 153 Such patients may perform above chancelevels on simple forced choice detection tasks, and on localisa-tion tasks in which the accuracy of finger pointing or eyemovements are taken as the index of perception for targetspresented in their scotoma. Weiskrantz expanded the defini-tion of blindsight to include visual capacity in a field defect inthe absence of acknowledged awareness.154 This definitionlacks the original anatomical specificity and covers forms ofnon-conscious visual processing that may have nothing to dowith lesions of V1. Subsequently, blindsight was applied tovisual perception in a neglected hemifield155 (such as inBlints patient) and can be taken to include knowledge with-out awareness in patients with agnosia for faces, although it isunclear what blindsight has to do with knowledge.

Current explanations for blindsight may be relevant toexplanations of visual performance in some patients withBlints syndrome. These explanations include residualfunction in visual pathways parallel to the retinogeniculostri-ate system including retinotectal, retinotectopulvinoextrastri-ate, and geniculoextrastriate pathways,153 156 residual striatecortex,157 158 or partial damage to cerebral networks servingvision.86 159 Striate cortex might be essential for consciousvisual perception160 or, alternatively, projections from extrastri-ate visual cortex to prefrontal cortex may suffice161; yet hemi-decorticated patients may retain some visual awareness,raising questions about both these mechanisms.162 The findingof residual vision in blindsight (and in purported cases ofAntons syndrome) could be due to test artifacts, such asinadequate fixation, light scatter, non-visual cues, andnon-random presentation of targets.157 The unawareness of thetargets presence distinguishes blindsight from residual vision.Those patients retain some awareness of the target within asupposedly dense visual field.163166 Vision without awarenessalso occurs in normal subjects.167 168

VISUALLY GUIDED REACHING AND OPTIC ATAXIABlints observations on optic ataxia1 sparked interest in theneural basis of visually guided reaching and grasping (fig 6).Reaching and grasping external objects is a fundamentalactivity that demands the coordination of several differentnervous system functions.95 169 To accomplish this task, thebrain transforms a targets visual coordinates to body centredspace, plans a hand path and trajectory (the sequence of handposition and velocity to target), and computes multiple jointtorques, especially about the shoulder and elbow. It also speci-fies the necessary limb segment orientations from amongmany possibilities, and activates appropriate muscle groupsand inhibits others to meet those specifications. The sensory

172 Rizzo, Vecera

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feedback, frames of reference and neural mechanisms used tosolve these complex motor control problems are activeresearch topics.170

Reaching can be divided into different phases. In atransport phase of reaching, the hand is moved toward anobject whose position is determined by vision or memory. Inan acquisition phase, grasp formation depends on somatosen-sory and visual information on the limb and target,171 famili-arity with the target and, perhaps, predetermined motor pro-grammes. These phases mature at different rates, may becontrolled independently before becoming coordinated,172 andcan be dissociated by focal brain lesions.94 96 99 173 Posteriorparietal damage may affect neurons coding eye position in thehead and stimulus location on the retina, which together withneurons in motor and premotor cortex permit hand move-ments to visual targets in a body centred coordinate system.170

The schema proposed by Soechting and Flanders174176 takesorigin at the shoulder, is closely related to the representationof object position and motion, and should depend on thevisual cortex and its connections to other sensory and motormaps.177179

Inability to reach and grasp targets in cases of Blints syn-drome is often multifactorial, including V1-type visual fielddefect, defective visual attention, inability to locate targetswith the eyes, and abnormal sensorimotor transformations. Arange of defects is possible, depending on the extent of apatients lesions. It seems that cerebral mechanisms forcontrolling pointing, reaching, and grasping depend on theinferior parietal lobule, temporoparietaloccipital junction,occipital-temporal cortices (particularly areas 37 and 21), andwhite matter connections. Current evidence suggests that: (1)separate systems exist within these regions to guide distanceand direction of reaching36 180; (2) if lesions of the occipital lobedo not extend into areas that project into dorsal stream path-ways to the posterior parietal cortex, they do not affect senso-rimotor transformations for reaching36 180; (3) superior andinferior parietal lobule lesions and lesions involving the dorsalvisual pathways cause abnormally large sensorimotor trans-formation errors36 181; and (4) mechanisms that control reach-ing are disturbed by V1 type visual dysfunction only if headand eye movements are constrained.180 182

Relevant to discussions of attention of Blints syndrome, itis possible that subjects with lesions in the dorsal visual path-way will have greater difficulty specifying target location whendistracters are present. Some types of distracters affect normalsubjects path and accuracy of reaching toward visualtargets.183 Distracters may strongly influence visual spatial

perception and/or movement control in subjects with lesionsof dorsolateral visual association cortices because theyincrease the complexity of the visual environment, increaseattention demands, and may interfere with the neural mecha-nisms underlying perception and movement planning andexecution of both reaching and grasping in normal youngadults. Distracters presented centrally,184 for example, but notperipherally185 in the visual field can also influence durationand path of a movement in normal controls. By contrast, onestudy found hand path deviation toward distracters presentedin the visual field ipsilateral to, but not contralateral to, a pari-etal lesion.186 Patterns of optic ataxia in Blints syndrome mayvary depending on whether a patient is reaching for a singleobject, or one object among many. Patterns of recovery in opticataxia have been reported by Goodale et al.99

Note that optic ataxia must sometimes be distinguishedfrom the alien hand phenomenon, in which a patient feelsestranged from one of his or her hands.187 The alien hand per-forms movements that seem beyond volitional control, as ifdriven by an external agent, and patients may try to restrain itusing the good limb. The defect is not just limited to reachingunder visual guidance. The affected hand may show a graspreflex and elements of what Denny-Brown referred to as amagnetic apraxia188 associated with frontal lobe damage.189

Optic ataxia may occur as part of Blints syndrome inAlzheimers disease, whereas the alien hand syndrome is morecharacteristic of cortical basal ganglionic degeneration. Char-acteristics of cortical basal ganglionic degeneration in 15patients included alien limb phenomena, apraxia, corticalsensory loss, focal reflex myoclonus, rigidity and akinesia,postural action tremor, limb dystonia, hyperreflexia, and pos-tural instability.190 Symptoms and signs are often asymmetric,with greater radiographic evidence of abnormalities in thehemisphere contralateral to the more affected limb. Neu-ropathological analyses may show swollen, poorly staining(achromatic) neurons and degeneration of the cerebral cortexand substantia nigra, and loss of striatal dopamine. Bycontrast, patients with Blints syndrome and optic ataxiashow histopathological changes compatible with Alzheimersdisease.23 24

Mechanisms of optic ataxia in patients with Blintssyndrome could overlap those of magnetic misreaching, as inMs D who had progressive parietal lobe degeneration andreached slavishly toward objects in central fixation whendirected to reach toward targets eccentric to fixation.191

Impaired reaching behaviours in Blints syndrome mayreflect the interaction among different hypothetical parietallobe and frontal lobe mechanisms for vision and action.192

Lesion of the right frontal lobe may impair monitoring ofinformation related to self generated arm movements.193 Theparietal cortex may sustain attention to stimuli in peripheralvision whereas the frontal lobe mediates selective attentionthrough habituation to peripheral stimuli,194 which mayexplain the fading of visual targets (the Troxler effect) experi-enced by patients with parietal lobe lesions as opposed tofrontal lobe lesions.193 Frontal lobe lesions may impair thesuppression of reflexive glances to peripheral stimuli (testedwith an anti saccade task) and initiation of voluntaryglances.195 The frontal lobes may aid in eliminating unwantedreflexive glances and in triggering new movements when thetarget is not yet known or visiblethat is, exerts control overa visual grasp reflex.195

CLINICAL APPROACHHolmes outlined a scheme for clinical investigations of visualfunctions of the nervous system that continues to be useful.8

He indicated that visual disorientation can be readily detected,but that it is critical to exclude visual field defects that mightinterfere with the interpretation. He recommended testing

Figure 6 Demonstration of optic ataxia in a patient with Blintssyndrome. The patient is unable to point to the tip of the examinersfinger and grossly overreaches (courtesy of Professor H StanleyThompson, Professor Emeritus, Ophthalmology, University of Iowa).

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acuity of central vision after errors of refraction had been cor-rected and opacities and other abnormalities of the mediahave been allowed for. These days, contrast sensitivity can alsobe tested (for example, with the Pelli-Robson wall chart). Hol-mes recommended screening the extent of visual fields forwhite and colours, firstly by confrontation methods and, ifneeded, by using a perimeter (to document the presence orabsence of visual field suspected by confrontation). He alsorecommended ophthalmoscopic evaluation, noting the edgesand central pit of each optic disc, the colour of each disc, thecondition of the retinae, particularly of the macular regions,and the state of the retinal vessels.

Holmes noted that disturbances of visual disorientation canbe detected by asking the patient to touch or point in thedirection of any objects within the range of vision and to esti-mate the distance from him by sight alone. He wrote: Relativelocalisation is tested by describing the relative positions inspace of two objects; when it is defective, he is unable to countcorrectly dots on a sheet of paper or coins scattered on a table,and he usually fails to divide a line accurately or find the cen-tre of a circle. If able to walk he should be required to find hisway about a room in which various obstacles, as chairs ortables, are placed, or through a house, and to describe a routewith which he is familiar. On attempting to read he often failsto follow the lines, and especially to bring his eyes to the leftof the succeeding line. Unilateral loss of orientation producesless obvious symptoms and is usually not recognised by thesubject, he is unable to point to or otherwise indicate, theposition of an object in the affected homonymous halves of thefields.8 Some modern laboratories are equipped to use

computerised psychophysical tests of attention and percep-tion; quantitative assessment of hand and eye movementsgenerally requires special equipment and expertise. Currentassessment would add relevant standardised neuropsycho-logical tests of visuoperceptual function, as in the case below.

A 70 year old right handed woman complained of increas-ing visual difficulties for 23 years. The patient had fallen onseveral occasions, and sometimes failed to recognise familiarsurroundings and became anxious and tearful. Severalophthalmological assessments showed no visual field deficitsand insufficient evidence of eye disease to account for visioncomplaints. The patient had increasing difficulty with dailyactivities. For example, after talking on the telephone she hadtrouble hanging up the receiver on its cradle. She could nolonger participate in her lifelong hobbies of sewing and oilpainting of pictures because her left arm was becoming diffi-cult to control and sometimes seemed to go off on its own. Shehad increasing difficulty following conversations and per-forming multistep commands. The patient had a history ofhypertension and hypothyroidism, but no stroke, seizure, orhead trauma. She had had a cholecystectomy, hysterectomy,and unilateral oophorectomy. The patients mother had expe-rienced depression, but there was no dementia, movementdisorder, or any other known neurological illness in the fam-ily. She had never obtained a drivers licence.

Examination showed an alert, socially appropriate olderwoman who appeared anxious but not acutely ill. She wasaware of and upset by her difficulties. She was oriented tomonth, city, and person, but not to the year or day of the week.She had striking difficulty with visuomotor tasks, such ascopying a simple line drawing of a geometrical figure. Speechwas fluent, but she had difficulty following two or more stepcommands. She scored 16/30 on the Mini Mental State Exam-ination, compatible with dementia of moderate severity.Cranial nerves were intact except for slight limitation ofupgaze. She had good muscle strength, but complained thather left hand wouldnt do what she wanted it to do. On oneoccasion her hand had seemed to levitate by her side. Shehad difficulty with skilled limb movements, especially withthe left. She had mild left hand dystonia. Visually guidedreaching was severely impaired, especially on the left, butthere was also some difficulty reaching to targets on her ownbody. Gait was slow and cautious, with reduced arm swing.She had difficulty locating and pointing towards a mirror on adoor in the examining room. While supine, upon command toraise her left leg, there was a delay of a few seconds before sheraised her right leg. Pinprick and touch were intact. Pallesthe-sia and proprioception were normal in the hand and feet. Ten-don stretch reflexes were graded as 2/2 and symmetric. Babin-skis sign was absent. There was no myoclonus or tremor.Haematological studies showed normal blood counts, thyroidfunctions, B12 and folate, liver function tests, and a rapidplasma reagin test was non-reactive.

Neuropsychological testing disclosed severe deficits on alltests involving ocular motor, visuospatial, and visuomotorabilities, including tests of constructional praxis, gesturalpraxis, visual scanning, manual dexterity, and visually guidedreaching (fig 7). The patient was unable to give a coherentreport of the Cookie Theft picture. She also had significantimpairments on tests of orientation, verbal memory, workingmemory, and speech and language (controlled word finding,aural comprehension, and confrontation naming). Electroen-cephalography showed slowing of the background rhythms inboth hemispheres, without epileptiform discharges or tripha-sic waves. Brain MRI was read as within normal limits for age.However, PET showed marked hypometabolism of bothparietal lobes (right greater than left), in the superior portionof both temporal lobes (right greater than left), and the lateraland midline portion of both occipital lobes. The basal gangliaand frontal lobes were intact. Transverse, coronal, and sagittalPET images are shown in figure 8.

Figure 7 Top panel: abnormal pointing movements are shownfrom a patient with features of Blints syndrome, in the context of thevisual variant of Alzheimers disease. The overhead view shows thepaths of multiple pointing movements between a target directly infront