Rehabilitating Patients With Left Spatial Neglect by Prism ExposureDuring a Visuomotor Activity

Paola FortisUniversity of Milano-Bicocca and S. Luca Hospital, Italian

Auxological Institute, Milan, Italy

Angelo Maravita and Marcello GallucciUniversity of Milano-Bicocca

Roberta RonchiUniversity of Milano-Bicocca and S. Luca Hospital, Italian

Auxological Institute, Milan, Italy

Elena GrassiCarlo Poma Hospital, Mantova, Italy

Irene SennaUniversity of Milano-Bicocca

Elena OlgiatiUniversity of Milano-Bicocca and Carlo Poma Hospital,

Mantova, Italy

Laura PeruccaUniversity of Milan, and S. Luca Hospital, Italian Auxological

Institute, Milan, Italy

Elisabetta BancoS. Luca Hospital, Italian Auxological Institute, Milan, Italy and

Maugeri Foundation, Pavia, Italy

Lucio PosteraroSuzzara Hospital, Suzzara, Italy

Luigi TesioUniversity of Milan, and S. Luca Hospital, Italian Auxological

Institute, Milan, Italy

Giuseppe VallarUniversity of Milano-Bicocca and S. Luca Hospital, Italian Auxological Institute, Milan, Italy

Objective: Adaptation to prisms displacing the visual scene rightward is a therapeutic tool for left unilateralspatial neglect (USN). We aimed at comparing the effects of the classic adaptation procedure (repeatedpointing toward visual targets, control treatment, C), with those of a novel adaptation method, involvingecological visuomotor activities (experimental treatment, E). Method: In 10 right-brain-damaged USNpatients, each treatment was given for 1 week, with a crossover design, for a total of 20 sessions, twice perday. USN was assessed by cancellation, reading, and drawing tasks, and by a standardized scale. Neurologicalseverity was assessed by the National Institutes of Health (NIH) stroke scale (Brott et al., 1989), disability bythe Functional Independence Measure (FIM) scale. Results: The 2-week treatments (EC, CE) were equallyeffective, improving both USN, confirming previous reports (Frassinetti, Angeli, Meneghello, Avanzi, &Ladavas, 2002) and, importantly, disability. The improvement was independent of baseline performance,duration of disease, and neurological severity. Recovery took place after the first week, continued in thesecond week, and was stable at the follow-up of 3 months. The improvement of USN, measured bycancellation performance, and, in part, that of disability, measured through the FIM scale, were mediated bythe size of the leftward aftereffects, suggesting a causal relationship between prism exposure and recovery.The E protocol was better tolerated. Conclusions: Daily life visuomotor activities, associated with prismexposure, are a useful tool for rehabilitating USN patients. This new treatment may widen the compliance withprism exposure treatments and their feasibility within home-based programs.

Keywords: visuospatial neglect, right hemisphere lesion, visually guided movement, adaptation, rehabilitation

Editor’s Note. Mark Mennemeier served as the action editor for thisarticle.—SMR

Paola Fortis, Roberta Ronchi, and Giuseppe Vallar, Department of Psychol-ogy, University of Milano-Bicocca and Neuropsychological Laboratory, S.Luca Hospital, Italian Auxological Institute, Milan, Italy; Angelo Maravita,Marcello Gallucci, and Irene Senna, Department of Psychology, University ofMilano-Bicocca; Elena Grassi, Neuromotor Rehabilitation Unit, Carlo PomaHospital, Mantova, Italy; Elena Olgiati, Department of Psychology, Universityof Milano-Bicocca and Neuromotor Rehabilitation Unit, Carlo Poma Hospital,Mantova, Italy; Laura Perucca and Luigi Tesio, Department of Physiology,University of Milan, and Clinic Department and Research Laboratory ofNeuromotor Rehabilitation, S. Luca Hospital, Italian Auxological Institute,

Milan, Italy; Elisabetta Banco, Neuropsychological Laboratory, S. Luca Hos-pital, Italian Auxological Institute, Milan, Italy and Neuromotor RehabilitationUnit, Maugeri Foundation, Pavia, Italy; and Lucio Posteraro, Department ofNeuromotor Rehabilitation, Suzzara Hospital, Suzzara, Italy.

This study was supported by a Grant (NESPA) from the Ministry of Health(ex. Art 56, 2005) to Giuseppe Vallar, Angelo Maravita, and Luigi Tesio; bya FIRST Project 2008 from the University of Milan to Laura Perucca and LuigiTesio, and by a Grant DDG 15315–2008 from the Lombardy Region. We aregrateful to Flavia Mancini for her support in the patients’ rehabilitation, and toMarius Peelen for his comments and suggestions.

Correspondence concerning this article should be addressed to GiuseppeVallar, MD, Department of Psychology, University of Milano-Bicocca,Building U6, Piazza dell’Ateneo Nuovo 1, 20126 Milan, Italy. E-mail:giuseppe.vallar@unimib.it

Neuropsychology © 2010 American Psychological Association2010, Vol. 24, No. 6, 681–697 0894-4105/10/$12.00 DOI: 10.1037/a0019476

681

Unilateral spatial neglect (USN) is a neuropsychological disor-der in which patients fail to report sensory events occurring in theportion of extrapersonal space and of the body contralateral to theside of the hemispheric lesion and to explore that part of space.USN is more frequent and severe after damage to the right cerebralhemisphere, involving the left side of space (Bisiach & Vallar,2000; Halligan, Fink, Marshall, & Vallar, 2003; Heilman, Watson,& Valenstein, 2003). The rate of occurrence after stroke variesconsiderably across studies (from 13% to 82%, with a medianof 43 in the review of Bowen, McKenna, & Tallis, 1999), mainlydepending on the test batteries adopted. Group studies indicatedthat left USN is a frequent deficit after right brain damage (mod-erate-to severe in 36% of the patients reported by Azouvi et al.,2002, with some degree of USN in 85% of the patients; 48%occurrence rate in the patients reported by Buxbaum et al., 2004).Right-brain-damaged USN patients present with a more severesensorimotor impairment than right-brain-damaged patients with-out USN (Buxbaum et al., 2004; Paolucci, Antonucci, Grasso, &Pizzamiglio, 2001). Finally, USN is associated with a more severeoverall disability, and is a predictor of poor functional outcomeafter right hemispheric stroke (Jehkonen, Laihosalo, & Kettunen,2006; Katz, Hartman-Maeir, Ring, & Soroker, 1999; Paolucci etal., 2001).

Lateralized physiological stimulations, including vestibular, op-tokinetic, transcutaneous electrical nervous, repetitive transcranialmagnetic, neck muscle vibration, DC brain polarization, andprisms that displace laterally the visual scene, may temporarilydecrease USN (Fierro, Brighina, & Bisiach, 2006; Kerkhoff, 2003;Ko, Han, Park, Seo, & Kim, 2008; Rossetti & Rode, 2002; Sparinget al., 2009; Vallar, Guariglia, & Rusconi, 1997). Some stimula-tions have been used for rehabilitation, resulting in improvementsof neuropsychological performance: neck muscle vibration (Schin-dler, Kerkhoff, Karnath, Keller, & Goldenberg, 2002), Transcuta-neous Electrical Nerve Stimulation (TENS) and optokinetic stim-ulation (Schroder, Wist, & Hömberg, 2008), and repetitive Trans-cranial Magnetic Stimulation (rTMS) (Brighina et al., 2003).

Adaptation to prisms displacing rightward the visual scenediminishes many manifestations of the USN syndrome, lasting forabout two hours and more (Rode, Klos, Courtois-Jacquin, Rossetti,& Pisella, 2006), although negative findings have been recorded(Rousseaux, Bernati, Saj, & Kozlowski, 2006). In addition to leftUSN, prism adaptation may also reduce drawing perseveration(Vallar, Zilli, Gandola, & Bottini, 2006, nine right-brain-damagedpatients with left USN), a productive phenomenon frequentlyassociated with USN (Na et al., 1999; Rusconi, Maravita, Bottini,& Vallar, 2002), although in one right-brain-damaged patient leftUSN decreased, but perseveration increased after prism exposure(Nys, Seurinck, & Dijkerman, 2008). One study showed thatadaptation to prisms displacing rightward the visual scene does notaffect the distribution of spatial attention in neurologically unim-paired participants (Experiment 1), and in four right-brain-dam-aged patients with left USN (Experiment 2); we find it interestingthat in two patients the rightward error in line bisection wasreduced by prism adaptation, but increased in one (Morris et al.,2004). These findings appear to indicate that the effects of prismadaptation are not mediated by a redistribution of spatial attention,but more recent evidence shows that prism adaptation may ame-liorate both visual search, provided search time is unlimited, and

USN, assessed by standard clinical tasks, with effects lasting atleast 2 hr (Saevarsson, Kristjansson, Hildebrandt, & Halsband,2009).

Due to these longer effects—compared to those of other ma-neuvers, that immediately fade away after the termination of thestimulation (optokinetic, muscle vibration), or typically last notmore than 30 min (vestibular, TENS), as well as to its completenoninvasiveness, prism adaptation is a suitable tool for the reha-bilitation of USN. Two studies in right-brain-damaged patients(Frassinetti, Angeli, Meneghello, Avanzi, & Ladavas, 2002, with acontrol group receiving no treatment for spatial neglect; Serino,Angeli, Frassinetti, & Ladavas, 2006) found that a 2-week treat-ment with prisms inducing a rightward shift decreased left USN, asassessed by visuospatial tests. The improvement involved bothperipersonal (Frassinetti et al., 2002) and personal space, tactileextinction, and persisted up to 6 months (Serino, Bonifazi, Pier-federici, & Ladavas, 2007). In right-brain-damaged patients withstroke, shorter 4-consecutive-days pointing sessions during prismexposure may improve left USN, as assessed by a cancellationtask, although at a 1-month assessment no difference was found,compared to a control group of patients who had worn neutralgoggles (Nys, de Haan, Kunneman, de Kort, & Dijkerman, 2008).The classic adaptation technique (Rossetti et al., 1998) involvesrepeated pointing to visual targets. In a rehabilitation setting, thistask has been repeated for 40 min per day for 2 weeks (Frassinettiet al., 2002; Serino et al., 2007). Left USN is decreased alsoafter 10 pointing sessions in which right-brain-damaged patientswear neutral goggles. More important, however, the improvementis greater when patients point to visual targets while wearingprisms producing a rightward shift (Serino, Barbiani, Rinaldesi, &Ladavas, 2009). This suggests a specific role of prism adaptation,over and above the positive effects of visuomotor activity per se.A negative finding is also on record. In a series of 34 right-brain-damaged patients (16 with prisms, 18 sham), a recent single-blinded randomized study found no effects of the prism treatmenton self care and left USN (Turton, O’Leary, Gabb, Woodward, &Gilchrist, 2009). However, this study used 6° rightward displacingprisms, which produced a minor displacement rather than the 10°prisms of the study by Frassinetti et al. (2002). Furthermore, therehabilitation procedure included 10 sessions (one per day), eachinvolving 90 pointing shots, as compared with the 20 sessionsadministered by Frassinetti et al. (2002). Accordingly, the negativefindings may reflect both the use of prisms producing a minorrightward shift, and the minor number of adaptation sessions (seehowever Serino et al., 2009, who reported a reduction of USNafter 10 pointing sessions during 2 weeks).

In this study, we compared the effects of adaptation achievedthrough pointing with a novel approach, characterized by visuo-motor activities, involving a variety of actions, common in dailyliving. We did not include an untreated control group. First, in acontrolled study it has been established that prism adaptationachieved through a pointing task is effective (Frassinetti et al.,2002). Similarly, an early study using Fresnel prisms found thatpatients wearing the prisms showed a greater improvement of USNand hemianopia, as compared with a control untreated group(Rossi, Kheyfets, & Reding, 1990). Second, a recent report showsthat 10 sessions of visuomotor pointing activity alone decrease leftUSN, yet the improvement is lower than the one achievable byprism adaptation through repeated pointing (Serino et al., 2009).

682 FORTIS ET AL.

Accordingly, we assessed whether visuomotor training, associatedwith prism exposure, was at least as effective as prism adaptationthrough pointing. We used a crossover design: Exposure to prismsdisplacing the visual scene toward the right side was associated tothe pointing adaptation treatment as the control (C) condition for 1week, and to the visuomotor activities as the experimental (E)condition for the other week, for a total of 2 weeks of treatment, asper the original studies (Frassinetti et al., 2002; Serino et al., 2007).

Method

Patients

A continuous series of 10 right-hemisphere-damaged patients(seven women, three men) with left USN entered this study.Patients were selected from the inpatient population of the Neu-rorehabilitation Unit of the Istituto Auxologico Italiano IRCCS,Milan, and the Neurorehabilitation Unit of the “Carlo Poma”Hospital, Bozzolo, Mantova, Italy. Patients gave informed consentto the study. The patients’ mean age was 72.7 years (SD � 5.19,range 66 to 82), and their mean education was 9.1 year(SD � 4.48; range 5 to 17). Patients were recruited during an18-months period (November 2006 to May 2008). Twelve right-brain-damaged patients with left spatial neglect did not enter thestudy, being unable to complete the baseline assessment, due to theseverity of their general medical condition. Four patients did notcomplete the study due to worsening of their general medicalcondition and to incapacity to cooperate (one patient). The 10patients’ average length of illness was 3.4 months (SD � 3.13,range 1 to 10). All patients were right-handed, according to astandard interview (Oldfield, 1971), and had no history or evidenceof previous neurological or psychiatric diseases. All patients had anormal or corrected-to-normal vision. The presence of visual fielddeficits was evaluated by a confrontation test (Bisiach & Faglioni,1974), and, in four out of 10 patients, also by computerizedperimetry. The etiology of the lesion was vascular in nine patients(eight ischemic, one hemorrhagic stroke), and neoplastic in onepatient (an operated benign tumor). The patients’ lesions wereassessed by CT scan in nine patients, and MRI scan in one patient.In patient FE the CT scan images, not available for mapping,showed an extensive cortico-subcortical ischemic fronto-temporo-parietal lesion, involving the basal ganglia and the insula. In nineout of 10 patients, the extent and the location of the lesions weredefined and visualized using MRIcro software (Rorden & Brett,2000). Lesions were drawn manually on an MRI template, usingthe closest matching transverse slice for each patient. Combiningall slices produced a 3-D lesion ROI for each patient. Figure 1shows the transverse sections of the ROIs. The patients’ lesionsoverlapped in the anterior and central white matter and in the basalganglia (head of the caudate nucleus, and pallidal nucleus). Thedemographic and neurological features of the patients are summa-rized in Table 1.

Neuropsychological Assessment and Functional Scales

Spatial neglect was assessed by standardized tests. All displayswere presented with their center aligned with the midsagittal planeof the trunk of participants, who used their right hand in thevisuomotor tasks. Spatial neglect is a multicomponent syndrome(Vallar, 1998), with the defective visuomotor exploration of near

extrapersonal space being its more frequently and extensivelyassessed manifestation, also in rehabilitation settings (Frassinetti etal., 2002; Pizzamiglio, Guariglia, Antonucci, & Zoccolotti, 2006;Serino et al., 2007). Accordingly, patients were classified as show-ing left neglect, when a defective performance was observed in atleast three out of the four tests of cancellation and drawing. Theneuropsychological battery tests and the three functional scales aredescribed in the following sections.

Cancellation tasks: Letter, bell, and star. In the letter task(Diller & Weinberg, 1977) the score was the number of “H” lettertargets crossed out by each participant (53 on the left-hand side and 51on the right-hand side of the sheet). Neurologically unimpairedparticipants made a mean of 0.13 (0.12%, SD � 0.45, range 0 to4) omission errors out of 104 targets, with the maximum differencebetween omissions on the two sides of the sheet being two targets(Vallar, Rusconi, Fontana, & Musicco, 1994). In the bell task(Gauthier, Dehaut, & Joanette, 1989) the score was the number of“bell” targets crossed out by each participant (18 on the left-handside and 17 on the right-hand side of the sheet). Neurologicallyunimpaired participants made a mean of 0.47 (1.3%, SD � 0.83,range 0 to 4) omission errors out of 35 targets, with the maximumdifference between omissions on the two sides of the sheet beingfour targets (Vallar et al., 1994). In the star task (Wilson, Cock-burn, & Halligan, 1987) the score was the number of small “star”targets crossed out by each participant (30 on the left-hand sideand 26 on the right-hand side). Ten neurologically unimpairedparticipants (mean age 72.2, SD 5.27, range 67 to 82; mean yearsof schooling 9.2, SD � 6.21, range 3 to 18) scored 0.5 averageomissions (0.9%, SD � 0.7, range 0 to 2), with the maximumdifference between omission errors on the two sides of the sheetbeing one target.

Figure 1. Lesion localization in nine right-hemisphere-damaged patients,and overlay lesion plots (bottom row: frequencies of overlapping lesions,from dark violet, n � 1, to orange, n � 8).

683NEGLECT, PRISM EXPOSURE, AND ECOLOGICAL ACTIVITIES

Five-element complex drawing (Gainotti, Messerli, & Tissot,1972). The patients’ task was to copy a complex five-elementfigure: from left to right, two trees, a house, and two pine trees.Each element was scored 2 (flawless copy), 1.5 ( partial omissionof the left-hand side of an element), 1 (complete omission of theleft-hand side of an element), 0.5 (complete omission of the left-hand side of an element, together with partial omission of theright-hand side of the same element), or 0 (no drawing, or norecognizable element). The total score ranged from 0 to 10. Ac-cording to normative data from 148 neurologically unimpairedparticipants (age: range 40 � 79; education: range 5 � 13 years ofschooling) a score lower than 10 indicated a defective performance(Corbetta, 2008).

Line bisection. For line bisection, the patients’ task was tomark with a pencil the midpoint of six horizontal black lines(two 10 cm, two 15 cm, and two 25 cm in length, all 2 mm inwidth), presented in a random-fixed order. Each line was printed inthe center of an A4 sheet, aligned with the midsagittal plane of theparticipant’s body. The length of the left-hand side of the line (i.e.,from the left end of the line to the participant’s mark) was mea-sured to the nearest millimeter. This measure was converted into astandardized score (percentage deviation), namely: measured lefthalf minus objective half/objective half � 100 (Rode, Michel,Rossetti, Boisson, & Vallar, 2006). This transformation yieldspositive numbers for marks placed to the right of the physicalcenter, negative numbers for marks placed to the left of it. Themean percentage deviation score of 65 neurologically unimpairedparticipants, matched for age (M � 72.2, SD � 5.16, range 65 to83), and years of education (M � 9.5, SD � 4.48, range 5 to 18)was �1.21% (SD � 3.48, range �16.2% to �6.2%; Corbetta,2008).

Word nonword reading test. This test included two listsof 19 words (List 1: M letter length 7.00, SD � 2.38; List 2: Mletter length 7.79, SD � 2.48), and 19 pronounceable nonwords(List 1: M letter length 7.47, SD � 2.61; List 2: M letterlength 7.37, SD � 2.36), taken from the set of Vallar, Guariglia,Nico, and Tabossi (1996). Each stimulus was printed in 18-pointArial font, uppercase, on a 13 � 18 cm construction paper. For

each list, the score was the number of incorrect responses (totalrange 0 to 38, for words and nonwords). Errors were classified asneglect-related errors by a “neglect point” measure (Ellis, Flude, &Young, 1987), namely: errors in which target and error stimuliwere identical to the right of an identifiable “neglect” point in eachitem, but shared no letters in common to the left of that point.Errors that did not meet the criteria for the neglect category wereclassified as “other” errors. Patients were considered as showingleft neglect dyslexia when more than 75% of their errors wereclassified as neglect errors. The two lists were alternately given toparticipants. Ten neurologically unimpaired participants, matchedfor age (M � 72.8 years, SD � 8.89, range 61 to 87), andeducation (M � 11.2 years, SD � 4.85, range 5 to 18) made noneglect errors on this test, and 0.95 (SD � 1.43, range 0 to 5) othererrors.

Sentence reading test (Pizzamiglio et al., 1992). This testincluded six sentences. The score was the number of incorrectlyread sentences (range 0 to 6). The neglect point score describedabove was used to classify reading errors as neglect and other. Tencontrol participants (see above, star cancellation) made no neglect,and 0.3 (5%, SD � 0.64, range 0 to 2) other errors.

Personal Neglect Test (after Bisiach, Perani, Vallar, & Berti,1986). In this test patients were asked to reach six left-sided bodyparts (ear, shoulder, elbow, wrist, waist, knee), using their righthand. Each response was scored 0 (no movement), 1 (searchwithout reaching), 2 (reaching with hesitation and search), or 3(immediate reaching), with a 0 to 18 score range. Ten controlparticipants (see above, star cancellation) made no errors.

Catherine Bergego Scale (CBS). This sensitive and reliable10-item scale (see Azouvi et al., 2003, for a description of thepsychometric properties) included: (a) the observation of the pa-tients’ behavior in standardized daily life tasks; and (b) a parallelself-administered form, designed as a questionnaire for an auto-evaluation made by the patients themselves. The scale was aimedat comparing activities in the right-hand and the left-hand sides ofthe patient’s body (e.g., “forgets to shave or groom the left part ofhis or her face”), and of extrapersonal space (e.g., “collides withpeople or objects on the left side”). Each item was rated on a scale

Table 1Demographic and Neurological Features of 10 Right-Brain-Damaged Patients With Left USN

Patient Age/sexLesion

etiologyEducation

(years)

Duration ofdisease

(months)

Neurological impairment

GroupMo SS VHF

BA 71/F H 13 2 � – – CEBG 79/M I 5 1 – ��� ��� CETA 71/F I 13 2 ��� �� ��/e CESG 82/F I 13 2 ��� �� e CEPF 66/F N 5 2a – e e CECF 75/M I 17 7 ��� ��� ��� ECFE 69/M I 5 1 ��� �� �� ECMF 71/F I 7 10 ��� e e ECRD 76/F I 8 1 – – – ECGMT 67/F I 5 6 ��� ��� e EC

Note. Mo � motor deficit; SS � somatosensory deficit; VHF � visual half-field deficit; F � female; H �hemorrhagic; plus sign (�) � mild deficit; minus sign (–) � absent deficit; CE � control experimental; M � male;I � ischemic; three plus signs (���) � severe deficit; two plus signs (��) � moderate deficit; e � extinction todouble simultaneous stimulation; N � neoplastic; EC � experimental control.a After neurosurgery.

684 FORTIS ET AL.

ranging from 0 (severe neglect) to 3 (no neglect), with a totalmaximum score of 30. The cumulative score was further classifiedas severe (Level 1: 0 to 10), moderate (Level 2: 11 to 20), and mild(Level 3: 21 to 30) neglect. The difference between the scoresrecorded in the parallel versions should provide, according to theauthors’ suggestion, an index of anosognosia for USN (see Azouviet al., 2003).

NIH stroke scale (Brott et al., 1989). This is a 15-item scaleassessing sensory-motor and cognitive functions, with scores(Items 1 to 13) ranging from 0 (normal) to 2 or 3 (maximalimpairment), for a total maximum score of 36.

FIM scale (The Guide for the Uniform Data Set for MedicalRehabilitation, 1997). This scale rated the patient’s indepen-dence in daily life (Tesio et al., 2002). The FIM scale included 13motor (e.g., dressing and walking), and five cognitive (e.g., com-prehension) items. Each item was rated based on a scale rangingfrom 1 (requiring total assistance) to 7 (completely independent).The scale gives rise to three cumulative scores: (a) the total score(18 items, range 18 to 126); (b) the motor score, assessing mobilityand locomotion (13 items, range 13 to 91); and (c) the cognitivescore, assessing communication and social cognition (five items,score 5 to 35).

The NIH and the FIM scales were administered by a physician,the CBS by an occupational therapist, both blind to the purpose ofthe study. The neuropsychological assessments were performed bya psychologist, distinct from the therapist or psychologist whoadministered the treatments, and blind to them as well. Throughoutthe time of the study all patients received a physical rehabilitationtreatment.

Rehabilitation Treatments

Pointing control treatment (Frassinetti et al., 2002). Thetreatment consisted in repeated pointing movements toward avisual target (the top of a red pen), using the right upper limb,placed inside a 32-cm high wooden box (see Figure 2). The lowerand the upper surfaces of the box had a pentagonal shape (74-cmlarge on the patient’s side, 19-cm high on the two sides, and 36-cmon the center). The box was open on the patient’s side (proximal).On the experimenter’s side (distal) it could be made either open(visible) or closed by a removable Plexiglas (invisible condition).

The target was presented in three positions on the distal side(straight ahead, 21° rightward, 21° leftward). In all conditions thethree positions of the target were assessed in a random-fixed order,with the same number of trials. The patients’ task was to point tothe target on the distal side of the box with their right index finger.Patients made a movement from the proximal side with their rightupper limb inside the box, starting from the middle of their chest,with no visual feedback. Pointing was performed in two condi-tions. In the visible condition, the distal side of the box was open,and patients saw their index finger emerging from it. In theinvisible condition, the distal side was closed, and the index fingerdid not show up. In both conditions, the vision of the proximal partof the patients’ upper limb was prevented by a cloth attached fromthe patients’ neck to the proximal side of the box. The distal edgeof the box and the removable Plexiglas were marked, on theexaminer’s side, to measure the patients’ pointing accuracy,namely the distance between their finger and the target, measuredin degrees (°). A positive score denoted a rightward displacementwith respect to the position of the target, a negative score aleftward displacement.

On the first day only, patients made 30 visible pointing trialsbefore starting the treatment. The pointing treatment consistedof 10 sessions (five in the morning, five in the afternoon, two perday), each including three conditions:

1. Pre-exposure: Immediately before wearing the pris-matic goggles: 30 invisible pointing trials. The experi-menter recorded the patient’s performance during thebeginning (1 to 3), and the end (28 to 30) three trials,each including one instance of the three target positions.

2. Exposure: While wearing the prismatic goggles: 90visible pointing trials, while the patients wore base-leftwedge prisms (Optique Peter, Lyon, France), that in-duced a 10° rightward shift of the visual field. Theexperimenter recorded the performance of each patientduring the beginning (1 to 3), middle (44 to 46), and end(88 to 90) three trials.

3. Postexposure: Immediately after the prismatic goggleshad been removed: 30 invisible pointing trials. Theexperimenter recorded the patient’s performance duringthe beginning (1 to 3) and the end (28 to 30) three trials.

The adaptation effect (the correction of the prism-induced lat-eral bias in pointing) was assessed comparing the errors in thebeginning, middle, and end triplets of pointing trials in the expo-sure visible condition. The completeness of adaptation (whether atthe end of the exposure visible condition, the error score wascomparable to that made in the pre-exposure baseline) was as-sessed comparing the pointing errors in the beginning three trialsof the pre-exposure visible condition and in the end three trials ofthe exposure visible condition.

The aftereffects (namely, the error observed immediately afterthe rightward-displacing prisms were taken off) were assessedcomparing the pointing error in three invisible conditions: thebeginning three trials of the pre-exposure condition, the beginningand the end three trials of the postexposure condition. The persis-tence of the aftereffects was the mean deviation in the beginning (1to 3) postexposure invisible trials minus the mean deviation in theend (28 to 30) postexposure invisible trials.

Figure 2. The box used for prism adaptation by repeated pointing trials,closed by the removable Plexiglas, seen from the examiner’s side. Marksfor the recording of the patients’ pointing errors are shown.

685NEGLECT, PRISM EXPOSURE, AND ECOLOGICAL ACTIVITIES

In addition to the adaptation and after effects measures for eachof the 10 sessions, 10-session effects measures were computed,averaging the adaptation effect, the aftereffects, and the persis-tence of the aftereffects scores across the 10 pointing sessions.

Finally, to assess the long-term effects of prism exposure, acrosssessions, the difference between the mean pointing error in the firstsession and in the last (10th) session of the pre-exposure invisibletrials was computed for each patient. If the aftereffects of prismadaptation build up across sessions, the leftward pointing errorshould be greater in the 10th session, compared to the first (long-term aftereffects).

The adaptation and aftereffects scores were recorded acrossthe 10 sessions of the control treatment with pointing, namelyin the control-experimental (CE) group during the first week, andin the experimental-control (EC) group during the second week.

To investigate the relationships between the adaptation and theaftereffects scores and the changes in the scores in the tests andscales during the C (pointing) treatment, mediational analyses forrepeated-measures designs were performed. These analyses wereperformed on the C treatment scores, because only for the pointingweek complete adaptation and aftereffects measures were avail-able. This method, based on regressing the change score of a testor scale, during the week in which patients received the C treat-ment, on the patients’ adaptation or aftereffect scores (the mediatorvariable), allowed estimating the degree by which the effect oftime (i.e., the improvement of the test or scale performance) wasrelated to the size of the adaptation or aftereffects. Based on themediation regression, the response to treatment (i.e., the scorechange during the treatment period) was considered as a mediatorwhen the B coefficient associated with it was statistically signifi-cant; the constant term of the regression (a: the intercept) estimatedthe amount of improvement for a treatment response equal to zero,namely, the amount of improvement not due to the treatmentresponse (Judd, Kenny, & McClelland, 2001). The mediationalanalyses were performed on the tests where a change during the Ctreatment was found.

Experimental Treatment

Patients sat at a table in front of the experimenter, and wore thebase-left wedge prisms, while performing daily life activities. Thenumber of sessions (n � 10), and the time of exposure tothe prismatic goggles for each session (20 min) were equal to thoseused in the pointing treatment. Patients were treated for 1 week,twice per day (morning and afternoon). Patients performed 12activities, consisting in the manipulation of common objects, ac-cording to the following sequence: (1) collecting coins on the tableand putting them in a money box, (2) dressing rings and bracelets,(3) opening and closing jars with the corresponding lids, (4)assembling three jigsaw puzzles, (5) assembling puzzles from theWechsler Adult Intelligence Scale (Wechsler, Coalson, & Raiford,2008), (6) box and block, (7) sorting and playing cards, (8)threading a necklace with 12 spools and a rope, (9) copying achessboard pattern on an empty chessboard, (10) serving a cup oftea, (11) WAIS Block Design, and (12) composing a dictated wordusing letters printed on squares. Typically, not all of the 12activities could be completed in one session. Accordingly, the nextsession started with the activity following the last performed in thesequence. The maximum time allotted to each task was 5 min, so

that each patient performed at least four activities. If the patientcompleted the task in less than 5 min, the next activity wasperformed. When patients stopped performing the task, or wereunable to complete one activity, the experimenter provided verbaland manual support for a maximum of three times each. If verbalprompts were ineffective, the examiner moved the patient’s handclose to the objects to-be-manipulated, but did not touch them.

Procedure

The neuropsychological and functional assessments were ad-ministered according to the following schedule:

• Assessments 1 to 3 (baseline, before the beginning of thetreatment): Assessments 1 and 2: 7 days before the study (one inthe morning, and one in the afternoon); Assessment 3: 7 days later,in the same day when the treatment was initiated; no scales wereadministered in Assessment 2.

• Assessment 4: At the end of the first week of treatment (Week 1).• Assessment 5: On the first day of the second week (Week 2).• Assessment 6: At the end of Week 2.• Assessment 7: At the beginning of Week 3.• Assessments 8, 9, and 10: 1, 2, and 3 months, after the end of

the treatment, respectively.

Patients were assigned to two groups: the CE group received thepointing task (control) in the first week, and the experimentaltreatment in the second week, the EC group vice versa. Patientswere alternately assigned to one of the two groups, starting withthe EC condition. Before starting the experimental treatment, thefive patients in the EC group received one half session of thepointing task: (1) pre-exposure visible pointing (15 trials), (2)pre-exposure invisible pointing (15 trials), (3) exposure visiblepointing (45 trials), and (4) postexposure invisible pointing (15trials). This session assessed the presence of prism adaptation andaftereffects in the week in which the EC patients received theexperimental treatment. At the end of the 2 weeks patients wereasked to communicate whether they had any preference concern-ing the two treatments and to make any comment they wished.

Statistical Design

In general, the effects of the two treatments over time wereassessed by repeated-measures analyses of variance (ANOVAs).To normalize the distribution of the patients’ scores in each test,percentage correct responses were converted in the arcsin of thesquare root of the raw values. The transformation improved thenormality of the score distribution, as evidenced by skewness andkurtosis values. For the NIH and the FIM scales the standardsummary score was used (Millis, Straube, Iramaneerat, Smith, &Lyden, 2007). Nonparametric statistical analyses (Siegel & Cas-tellan, 1988) were performed on the CBS scores due to the pres-ence of ordinal scaling and on the personal neglect test due todistributional concerns. For the ANOVAs, group (CE, EC) was themain between-subjects factor, and time (average baseline, Week 1,and Week 2) was the main within-subjects factor. The Week 1 andWeek 2 scores were the means of the assessments performed at theend of each week (Week 1: Assessments 4 to 5; Week 2: Assess-ments 6 to 7). In each test and scale, significant differences werefound neither in the Week 1 (4 and 5) nor in the Week 2 (6 and 7)assessments.

686 FORTIS ET AL.

The adaptation and aftereffects were analyzed by ANOVAs,with the between-subjects main factor group, and these within-subjects main factors: pointing error (in the different exposureconditions, and in the different phases of the trial sequence [be-ginning, middle, end], averaged across the three positions of thetarget), Session (1 through 10).

Significant differences were explored by Newman–Keuls’s posthoc multiple comparisons.

Effects were evaluated also according to their standardizedeffect size index. The partial eta-squared (�p

2) was selected as theindex (Cohen, 1973).

One-Week Stability of the Deficit Before Treatment

The enrolment of the patients in the present study was pseudo-randomized, based on the alternate assignment to one of the twogroups (CE, EC). A limited matching between the two groups,particularly for USN and stroke severity, is of concern. To assessthe stability of USN before treatment, one-way repeated-measuresANOVAs were performed on the baseline scores (percentagecorrect responses, converted into the arcsin of the square root ofthe raw values) of the diagnostic tests. No differences were foundfor the letter, F(2, 9) � 1.58, p � .23, �p

2 � .150; star, F(2,5) � 0.51, p � .61, �p

2 � .16; and bell, F(2, 9) � 2.93, p � .08,�p

2 � .245; cancellation, as well as for the drawing, F(2, 9) � 1.05,p � .37, �p

2 � .104 tests. No differences in the baseline scoreswere found for the NIH, F(1, 9) � 1.00, p � .34, �p

2 � .100; FIM,F(1, 9) � 1.01, p � .34, �p

2 � .100; and CBS scales (Wilcoxon’smatched pairs test, T � 0, p � .10).

However, differences between groups cannot be completelyruled out, because the limited number of participants in each groupmight provide insufficient power to detect a significant difference.

To further control for possible effects of the baseline level ofperformance on the outcome of the treatment, the baseline scorewas used as a covariate variable. For each test and scale (summaryscores), a one-way repeated-measures analysis of covariance(ANCOVA) was performed on time (scores of Week 1 and Week2), with the baseline score (the centered mean score of the threebaselines) as a linear and interactive covariate. The interactionterm was introduced to test for the applicability of the ANCOVAmodel (Cohen, West, Cohen, & Aiken, 2002; Rogosa, 1980). Thecovariate was centered to its mean to allow interpreting the treat-ment effect in the presence of the interaction term (Aiken & West,1991). Finally, two ANCOVAs were performed on the scoresobtained by the two patients’ groups (EC, CE) in the 2 weeks oftreatment (baseline, Week 1, Week 2), using the standardized NIHscale baseline score and the duration of disease as linear andinteractive covariates. These analyses explored the possibility thatbaseline neurological severity and duration of disease influencedchanges of the patients’ scores in the tests and scales during thetreatment.

Results

Neuropsychological Tests and Neurological andFunctional Scales

Tables 2 and 3 show the patients’ performances in the threeassessments, in the cancellation tasks, in the complex drawing, andsentence reading tasks, and in the NIH and FIM scales. The mainresult is that the patients’ performance improved during the 2weeks of treatment (i.e., the time main factor was significant in allanalyses), independent of their assignment to the CE or EC group(i.e., the group factor and the Time � Group interaction were not

Table 2Neuropsychological Scores (SEM in Brackets) in the Baseline (B), Week 1 (W1), and Week 2 (W2) Assessments, by Group

Task

Time ANOVA

B W1 W2 Time Group Time � Group Post hoc

LC F � 14.82 F � 3.02 F � 1.77 B–W1��

CE .65 (.04) .70 (.03) .86 (.03) p � .001 p � .12 p � .20 B–W2���

EC 0.32 (.03) .56 (.05) .67 (.05) �p2 � .65 �p

2 � .27 �p2 � .18 W1–W2��

BC F � 13.89 F � 0.37 F � 2.52 B–W1�

CE .45 (.07) .52 (.07) .59 (.06) p � .001 p � .06 p � .11 B–W2���

EC .23 (.03) .41 (.04) .59 (.06) �p2 � .63 �p

2 � .04 �p2 � .24 W1–W2�

SC F � 6.00 F � 0.02 F � 1.86 B–W2�

CE .55 (.08) .63 (.09) .66 (.07) p � .05 p � .89 p � .21EC .57 (.13) .60 (.10) .74 (.13) �p

2 � .55 �p2 � .01 �p

2 � .27CD F � 8.52 F � 3.99 F � 1.03 B–W2��

CE .92 (.01) .90 (.02) .98 (.01) p � .01 p � .08 p � .38 W1–W2��

EC .55 (.07) .65 (.07) .76 (.05) �p2 � .52 �p

2 � .33 �p2 � .11

SR F � 5.00 F � 1.60 F � 2.10 B–W1†

CE .12 (.03) .02 (.01) .05 (.01) p � .05 p � .24 p � .16 B–W2�

EC .34 (.08) .30 (.07) .18 (.07) �p2 � .38 �p

2 � .17 �p2 � .21

LB F � 0.48 F � 3.26 F � 0.82CE .06 (.02) .03 (.04) .03 (.02) p � .63 p � .11 p � .46EC .10 (.05) .13 (.04) .08 (.02) �p

2 � .05 �p2 � .29 �p

2 � .09

Note. For the analysis of variance (ANOVA): the degrees of freedom were (2, 16) for the time main factor and for the Time � Group interaction, (1,8) for the group main factor, and (2, 10; 1, 5) for star cancellation, percentage correct (SC). LC � letter cancellation, percentage correct; CE � controlexperimental; EC � experimental control; BC � bell cancellation, percentage correct; CD � complex drawing, percentage correct; SR � sentence reading,percentage error; LB � line bisection, percentage deviation.† p � .06. � p � .05. �� p � .01. ��� p � .001.

687NEGLECT, PRISM EXPOSURE, AND ECOLOGICAL ACTIVITIES

significant). In the line bisection task the patients’ performance didnot change during the 2 weeks of treatment.

One out of 10 patients showed left neglect dyslexia for singlewords and nonwords. FE made an average of 22 neglect errors outof the 38 word and nonword stimuli (57%) in the baseline sessions,five errors (12%) at the end of Week 1, �2(1) � 14.71, p � .001,and zero at the end of Week 2, �2(1) � 28.21, p � .001.

Four out of 10 patients (three in the CE group and one in the ECgroup) exhibited personal USN in the baseline, and in all of themthe deficit had improved at the end of Week 2. The scores of the 10patients were 17.32 (SD � 1.46) out of 18 (96.2%), 17.85(SD � 0.33; 99.1%), and 17.95 (SD � 0.15; 99.7%), in thebaseline, Week 1, and Week 2 assessments. A Friedman ANOVAshowed a difference among these assessments, �2(2) � 9.5, p �.01. The scores of the four patients with personal USN were 15.74(SD � 1.62; 87.4%), 17.63 (SD � 0.48; 97.94%), and 17.88(SD � 0.25; 99.33%) in the baseline, Week 1, and Week 2assessments.

The CBS scale was administered to nine out of 10 patients. Thepatients’ scores were 1.77 (SD � 0.83) in the baseline, 2.33(SD � 0.87) at the Week 1, and 2.55 (SD � 0.53) at the Week 2assessments. A Friedman ANOVA revealed a significant differ-ence among assessments, �2(2) � 11.14, p � .01. Multiple com-parisons showed a significant difference between baseline andWeek 2 ( p � .05). In the baseline, USN was severe in fourpatients, moderate in three, and mild in two. After 1 week oftreatment, two patients showed a severe, two a moderate, and fivea mild USN. After 2 weeks USN was mild in five patients, andmoderate in four, with no patient showing a severe USN. In sum,in seven out of nine patients USN improved after the 2 weeks,being already mild in the baseline in two patients. The differencebetween the score of the CBS scale and the questionnaire ofself-evaluation provided an index of the patients’ awarenessof USN. Two out of nine patients (MF, RD) proved to be aware ofUSN, as indexed by a score lower in the self-rated, compared tothe observer-rated version of the test. The seven anosognosic

patients scored 15.78 (SD � 9.17) in the baseline, 10.71(SD � 8.12) at the Week 1, and 8.64 (SD � 6.39) at the Week 2assessments. A Friedman ANOVA showed a significant differ-ence, �2(2) � 6, p � .05. Multiple comparisons revealed a signif-icant difference between baseline and Week 2 ( p � .05). A perusalof the individual data showed that in six out of seven patients theanosognosia score diminished from the baseline to Week 1 andfrom Week 1 to Week 2. One patient (CF) did not show anyimprovement of the anosognosia score.

Baseline Performance and Treatment Effects

Table 4 shows the main effects of time and group, the Time �Group interaction, the effect of baseline and the Time � Baselineinteraction. For the letter and bell cancellation and the complexdrawing tasks, and for the CBS and FIM scales, the main effect oftime was significant, while the Time � Group interaction and,crucially, the Baseline � Time interaction were not. The nonsig-nificant Baseline � Time interaction indicates that the improve-ment during the Week 1 to Week 2 time period of treatment (i.e.,the time effect) was not dependent on the baseline level of per-formance. Therefore, any group difference present at the baselinetime did not influence the improvement over the Week 1 to Week 2time period.

For the sentence reading test not only the time main factor, butalso the Time � Group interaction was significant, while theTime � Baseline interaction was not. This result shows a differ-ential improvement in the two groups (EC, CE) between Week 1and Week 2. This may be traced back to differences in theperformance levels of the two groups. The mean number of errorsat the end of Week 1 and Week 2 were 2% and 5% for Group CE,30% and 18% for Group EC (see Table 2). These scores, however,albeit different, were not affected by the baseline scores. For thestar cancellation task the main effect of time, the Group � Time,and the Baseline � Time interactions were not significant. Thistest was given to only seven participants (four patients in the CE

Table 3NIH and FIM Summary Scores (SEM in Brackets) in the Baseline (B), Week 1 (W1), and Week 2 (W2) Assessments, by Group

Task

Time ANOVA

B W1 W2 Time Group Time � Group Post hoc

NIH F � 5.00 F � 1.21 F � 0.89 B–W1�

CE 14.51 (1.57) 12.40 (2.42) 10.60 (2.18) p � .05 p � .30 p � .43 B–W2�

EC 9.80 (1.28) 8.60 (1.83) 7.60 (1.75) �p2 � .35 �p

2 � .13 �p2 � .10

FIMMotor F � 15.31 F � 0.16 F � 0.75 B–W1�

CE 32.60 (8.91) 37.60 (9.53) 39.20 (9.93) p � .001 p � .70 p � .49 B–W2���

EC 35.10 (6.23) 38.34 (8.06) 42.90 (9.95) �p2 � .66 �p

2 � .02 �p2 � .09 W1–W2�

Cognitive F � 4.73 F � 3.90 F � 0.94 B–W2�

CE 18.60 (2.25) 20.21 (2.27) 22.80 (3.48) p � .05 p � .08 p � .41EC 28.00 (1.76) 28.54 (1.92) 28.80 (0.97) �p

2 � .37 �p2 � .33 �p

2 � .11Total F � 14.45 F � 0.75 F � 0.38 B–W1�

CE 51.20 (7.52) 57.81 (8.06) 62.00 (7.39) p � .001 p � .41 p � .68 B–W2���

EC 63.10 (7.43) 66.88 (9.12) 71.70 (10.53) �p2 � .65 �p

2 � .09 �p2 � .05 W1–W2��

Note. For the analysis of variance (ANOVA): the degrees of freedom were (2, 16) for the time main factor and for the Time � Group interaction and(1, 8) for the group main factor. NIH � National Institutes of Health stroke scale; FIM � Functional Independence Measure scale; CE � controlexperimental; EC � experimental control.� p � .05. �� p � .01. ��� p � .001.

688 FORTIS ET AL.

group, three in the EC group), possibly reducing the power todetect significant differences. For the line bisection task, theANCOVA confirmed the lack of improvement during the treat-ment.

For the NIH scale, the main effect of time was not significant,while the Time � Baseline, and the Time � Group interactionswere significant or marginally significant. These findings indicatethat the improvement of the NIH scale scores during the Week 1to Week 2 treatment period depended on the baseline level. Aperusal of the data showed that the improvement was larger for thehigher baseline NIH scores, namely in the patients with a moresevere deficit. In sum, these findings show that the patients’improvement in the NIH scale was dependent on the baseline levelof performance, suggesting that the scores’ changes in the Week 1to Week 2 treatment period reflect factors different from the prismtreatment, such as spontaneous recovery, or the effects of physio-therapy. This was not the case of the patients’ improvement in theneuropsychological tests and in the FIM and CBS scales, whichwere unaffected by the baseline level of performance.

Neurological Factors and Recovery From USN AfterPrism Adaptation: NIH Scale

To control whether the baseline level of neurologic severity mayhave influenced the outcome of the 2-week prism adaptation

treatment, the standardized baseline NIH score was used as acovariate variable. For each test and scale, repeated-measuresANCOVAs were performed, with time (scores at baseline,Week 1, and Week 2) as a within-subjects factor, and group (EC,CE) as a between-subjects factor. As Table 5 shows, for each testand scale the main effect of time was significant, while theGroup � Time, and the Time � NIH baseline score interactionswere not significant. These results, particularly the lack of inter-action between the time and NIH baseline factors, show that bothgroups improved over time, independent of the patients’ initialneurologic severity. This makes unlikely an interpretation of therecovery of USN during the prism adaptation treatment as anaspect of general neurologic recovery.

Duration of Disease

To control whether the distance from the onset of the neurolog-ical disease (see Table 1) may have influenced the outcome of the2-week prism adaptation treatment, the standardized duration ofdisease, expressed in months, was used as a covariate variable. Foreach test and scale, repeated-measures ANCOVAs were per-formed, with the time and group factors used in the ANCOVAsreported above. Table 6 shows that in the letter and star cancella-tion, complex drawing, sentence reading tasks, and in the scales,the main effect of time was significant, while the Time � Group

Table 4Repeated-Measures Analysis of Covariances With a Within-Subjects Factor, Time (Scores Week 1 and Week 2), and a Between-Subjects Factor, Group (CE and EC), With the Standardized Baseline Mean Score as a Linear and Interactive Covariate

Test Time Group Baseline Time � Group Time � Baseline

LC F � 8.03, p � .05 F � 0.65, p � .45 F � 5.85, p � .05 F � 0.26, p � .88 F � 0.142, p � .72BC F � 7.59, p � .05 F � 2.21, p � .18 F � 20.98, p � .05 F � 0.93, p � .37 F � 0.04, p � .86SC F � 3.46, p � .136 F � 0.14, p � .91 F � 39.65, p � .05 F � 2.55, p � .19 F � 0.08, p � .79CD F � 7.75, p � .05 F � 0.11, p � .75 F � 22.85, p � .05 F � 0.36, p � .57 F � 0.85, p � .39SR F � 5.95, p � .05 F � 0.78, p � .41 F � 35.12, p � .05 F � 23.1, p � .01 F � 0.24, p � .64LB F � 1.33, p � .29 F � 3.03, p � .12 F � 1.64, p � .24 F � 7.58, p � .41 F � 1.00, p � .35CBS F � 14.77, p � .05 F � 0.30, p � .60 F � 20.47, p � .05 F � 1.80, p � .22 F � 1.58, p � .25FIM F � 12.42, p � .05 F � 0.81, p � .40 F � 59.54, p � .001 F � 0.12, p � .74 F � 0.02, p � .88NIH F � 0.74, p � .74 F � 2.80, p � .14 F � 16.33, p � .01 F � 5.13, p � .06 F � 6.65, p � .05

Note. The degrees of freedom were (1, 7) for all analyses except the star test (1, 4), time main factor, and the interactions, and (1, 3) baseline covariate.CE � control experimental; EC � experimental control; LC � letter cancellation, percentage correct; BC � bell cancellation, percentage correct; SC �star cancellation, percentage correct; CD � complex drawing, percentage correct; SR � sentence reading, percentage error; LB � line bisection, percentagedeviation; CBS � Catherine Bergego scale; FIM � Functional Independence Measure scale; NIH � National Institutes of Health stroke scale.

Table 5Repeated-Measures Analysis of Covariances With a Within-Subjects Factor, Time (Scores Baseline, Week 1, and Week 2), and aBetween-Subjects Factor, Group (CE and EC), With the Baseline NIH Score as a Linear and Interactive Covariate

Test Time Group NIH score Time � Group Time � NIH score

LC F � 14.49, p � .001 F � 5.75, p � .05 F � 2.30, p � .17 F � 1.78, p � .20 F � 0.79, p � .47BC F � 12.55, p � .01 F � 5.38, p � .054 F � 7.07, p � .05 F � 0.73, p � .50 F � 0.36, p � .70SC F � 4.95, p � .05 F � 0.476, p � .53 F � 0.97, p � .38 F � 1.13, p � .37 F � 1.00, p � .41CD F � 9.27, p � .01 F � 2.41, p � .16 F � 0.03, p � .87 F � 2.59, p � .11 F � 0.25, p � .21SR F � 4.86, p � .05 F � 1.68, p � .24 F � 0.34, p � .58 F � 3.27, p � .07 F � 0.21, p � .81LB F � 0.45, p � .65 F � 1.13, p � .32 F � 0.17, p � .69 F � 0.59, p � .57 F � 0.56, p � .58CBS F � 24.89, p � .001 F � 0.12, p � .91 F � 0.20, p � .67 F � 2.23, p � .14 F � 2.95, p � .08FIM F � 15.73, p � .001 F � 0.44, p � .53 F � 5.70, p � .05 F � 1.54, p � .25 F � 1.44, p � .27

Note. Degrees of freedom were (2, 14) for the time main factor and the interactions; (1, 7) for the group main factor and the NIH covariate; and (2, 8)and (1, 4) for the star test. CE � control experimental; EC � experimental control; NIH � National Institutes of Health stroke scale; LC � lettercancellation, percentage correct; BC � bell cancellation, percentage correct; SC � star cancellation, percentage correct; CD � complex drawing,percentage correct; SR � sentence reading, percentage error; LB � line bisection, percentage deviation; CBS � Catherine Bergego scale; FIM �Functional Independence Measure scale.

689NEGLECT, PRISM EXPOSURE, AND ECOLOGICAL ACTIVITIES

and the Time � Duration of Disease interactions were not signif-icant. For the bell task, the main effect of time, and the Time �Group interaction were significant, while the Time � Duration ofDisease interaction was not significant. This result suggests thatduration of disease did not influence the patients’ improvement inthe bell task, while a different effect of time was found in the twogroups (CE and EC). This might have been caused by baselinedifferences between the two groups. To test for this hypothesis, arepeated-measures ANCOVA with time (scores at Week 1 andWeek 2) as a within-subjects factor, and group as a between-subjects factor was performed, with the standardized duration ofdisease and the standardized baseline as covariate variables. Themain effect of time, F(1, 7) � 8.23, p � .05, was still significant,while the main effect of group, F(1, 6) � 5.27, p � .61, was notsignificant as well as crucially, the Group � Time interaction, F(1,7) � 1.59, p � .26. These results show that also in the bell testboth groups improved over time, independent of the duration ofdisease.

Control Pointing Task

Adaptation. Figure 3 shows that adaptation took place in thefirst 45 pointing trials of each session, with a reduction of therightward error. An ANOVA with the between-subjects factorgroup, and two within-subjects factors (session of treatment [1 to10]; pointing error: beginning [1 to 3], middle [44 to 46], and end[88 to 90] trials) showed that the main effect of pointing error wassignificant, F(2, 16) � 17.74, p � .001, �p

2 � .680; while neitherthe group, F(1, 8) � 0.06, p � .81, �p

2 � .007; nor the session, F(9,72) � 0.48, p � .88, �p

2 � .056; main effects were significant aswell as the Group � Session, F(9, 72) � 0.86, p � .56, �p

2 � .097;the Group � Pointing Error, F(2, 16) � 0.33, p � .72, �p

2 � .039;the Pointing Error � Session, F(18, 144) � 0.59, p � .90, �p

2 �.068; and the Group � Session � Pointing Error, F(18,144) � 1.03, p � .42, �p

2 � .114 interactions. Multiple compari-sons showed significant differences between the beginning andmiddle ( p � .001), and the beginning and end ( p � .001) trials.The difference between the middle and end trials was not signif-icant ( p � .68). The completeness of adaptation was assessed byanalyzing whether the pointing error in the visible condition was

comparable before adaptation, and at the end of it. The error scoresin the beginning trials (1 to 3) of the pre-exposure visible condi-tion, and in the end trials (88 to 90) of the exposure visiblecondition, averaged across the 10 visible exposure sessions, werecompared in the two groups. The main effects of group, F(1,8) � 0.14, p � .71, �p

2 � .017; and of pointing error, F(10,80) � 0.57, p � .83, �p

2 � .065; were not significant as well as theGroup � Pointing Error interaction, F(10, 80) � 1.38, p � .20,�p

2 � .147. The scores in the beginning trials of the pre-exposurevisible condition were �0.93° (SEM � 0.36) in Group CE,and 2.73° (SEM � 0.80) in Group EC. The scores in the end trialsof the exposure visible condition were 2.02 (SEM � 0.06) inGroup CE, and 2.20 (SEM � 0.07) in Group EC. No differences inprism adaptation related to the presence/absence of visual half-field deficits were found. An ANOVA with the between-subjectsfactor group (patients with, n � 4, and without, n � 6, a left visualhalf-field deficit, see Table 1), and two within-subjects factors (ses-sion of treatment [1 to 10]; pointing error [beginning, middle, and endtrials of the exposure visible condition]) showed a significant maineffect of pointing error, F(2, 16) � 16.20, p � .001, �p

2 � .669. Themain effects of group, F(1, 8) � 0.42, p � .52, �p

2 � .049; and ofsession, F(9, 72) � 0.50, p � .86, �p

2 � .058; were not significantas well as the Group � Pointing Error, F(2, 16) � 0.48, p � .62,�p

2 � .056; the Pointing Error � Session, F(18, 144) � 0.70, p �.81, �p

2 � .086; the Group � Session, F(9, 72) � 1.20, p � 0.30,�p

2 � .130; and the Group � Session � Pointing Error, F(18,144) � 1.61, p � .06, �p

2 � .167 interactions.Aftereffects. As Figure 4 shows, the aftereffects after the

removal of the prisms (namely the difference between the pointingerrors during invisible pointing, before and after adaptation) werecomparable in the two groups. An ANOVA with the between-subjects factor group, and two within-subjects factors (session [1 to10]; pointing error: beginning [1 to 3] trials of the pre-exposureinvisible condition, beginning [1 to 3] and end trials [28 to 30] of thepostexposure invisible condition) showed a significant main effect ofpointing error, F(2, 16) � 26.20, p � .001, �p

2 � .766. The maineffects of group, F(1, 8) � 0.98, p � .35, �p

2 � .109; and ofsession, F(9, 72) � 1.96, p � .06, �p

2 � .196 were not significant.The Group � Session, F(9, 72) � 1.27, p � .26, �p

2 � .137; the

Table 6Repeated-Measures Analysis of Covariances With a Within-Subjects Factor, Time (Scores Baseline, Week 1, and Week 2), and aBetween-Subjects Factor, Group (CE and EC), With Duration of Disease as a Linear and Interactive Covariate

Test Time Group Duration of disease Time � Group Time � Duration of disease

LC F � 14.22, p � .001 F � 1.43, p � .27 F � 0.10, p � .76 F � 9.82, p � .40 F � 0.64, p � .54BC F � 16.44, p � .001 F � 0.11, p � .75 F � 0.82, p � .78 F � 5.42, p � .05 F � 2.64, p � .11SC F � 8.17, p � .05 F � 0.60, p � .82 F � 0.50, p � .83 F � 2.99, p � .11 F � 1.94, p � .21CD F � 9.27, p � .01 F � 3.58, p � .10 F � 0.29, p � .61 F � 0.89, p � .43 F � 1.72, p � .21SR F � 4.75, p � .05 F � 3.12, p � .12 F � 1.61, p � .24 F � 2.45, p � .12 F � 0.05, p � .95LB F � 0.54, p � .60 F � 1.31, p � .29 F � 0.32, p � .59 F � 2.33, p � .13 F � 2.06, p � .16CBS F � 22.83, p � .001 F � 0.05, p � .94 F � 0.23, p � .65 F � 0.30, p � .75 F � 2.13, p � .16FIM F � 14.92, p � .001 F � 4.88, p � .06 F � 5.73, p � .05 F � 0.00, p � .10 F � 1.00, p � .39NIH F � 4.76, p � .05 F � 2.34, p � .17 F � 1.23, p � .30 F � 0.23, p � .80 F � 0.69, p � .52

Note. Degrees of freedom were (2, 14) for the time main factor and the interactions; (1, 7) for the group main factor and the NIH covariate; and (2, 8)and (1, 4) for the star test. LC � letter cancellation, percentage correct; BC � bell cancellation, percentage correct; SC � star cancellation, percentagecorrect; CD � complex drawing, percentage correct; SR � sentence reading, percentage error; LB � line bisection, percentage deviation; CBS � CatherineBergego scale; FIM � Functional Independence Measure scale; NIH � National Institutes of Health scale.

690 FORTIS ET AL.

Group � Pointing Error, F(2, 16) � 0.80, p � .46, �p2 � .090; the

Pointing Error � Session, F(1, 8) � 0.14, p � .71, �p2 � .017; and

the Group � Session � Pointing Error, F(18, 144) � 1.34, p �.17, �p

2 � .143 interactions were not significant. Multiple compar-isons revealed that the mean error in the beginning trials of thepostexposure invisible condition (�4.54°, SEM � 0.95) differedfrom those of both the beginning trials of the pre-exposure invis-ible condition (�2.26°, SEM � 0.76, p � .001), and the end trials(�3.3°, SEM � 0.99) of the postexposure invisible condition ( p �.01). The difference between the beginning trials of the pre-exposure condition and the end trials of the postexposure conditionwas also significant ( p � .01). Exposure to prisms displacing thevisual scene rightward brought about aftereffects in the oppositeleftward direction, which diminished in size during the postexpo-

sure period. At variance with the present findings, Frassinetti et al.(2002) found no difference in the size of the aftereffects betweenthe first three (�1.7°) and the last three (�1.8°) trials of thepostexposure invisible condition. The size of the leftward afteref-fects was however larger in the present study (first three trials:�4.5°, last three trials: �3.3°). The aftereffects were not affectedby the presence/absence of visual half-field deficits. An ANOVAwith the between-subjects factor group (patients with and without aleft visual half-field deficit), and two within-subjects factors (session[1 to 10]; pointing error: beginning trials of the pre-exposure invisiblecondition, beginning, and end trials of the postexposure invisiblecondition) showed a significant main effect of pointing error, F(2,16) � 23.62, p � .001, �p

2 � .747. The main effects of group,F(1, 8) � 0.59, p � .46, �p

2 � .068; and of session, F(9,72) � 1.62, p � .13, �p

2 � .168 were not significant. The Group �Session, F(9, 72) � 0.93, p � .50, �p

2 � .104; the Group �

Figure 3. Adaptation effect: Visible condition. Pointing error (degrees,SEM; positive/negative scores indicate rightward/leftward errors) in thebeginning, middle, and end trials, by group. EC � experimental control;CE � control experimental.

Figure 4. Aftereffects: Invisible condition. Pointing error (see Figure 3)in the pre-adaptation beginning trials and in the postadaptation beginningand end trials, by group. EC � experimental control; CE � controlexperimental.

691NEGLECT, PRISM EXPOSURE, AND ECOLOGICAL ACTIVITIES

Pointing Error, F(2, 16) � 0.80, p � .47, �p2 � .090; and the

Pointing Error � Session, F(18, 144) � 0.76, p � .74, �p2 � .086;

as well as the Group � Session � Pointing Error, F(18,184) � 1.36, p � .16, �p

2 � .117 interactions were not significant.As for the long-term aftereffects, the error in the invisible pre-exposure pointing trials was �0.43° (SEM � 0.46) in the firstsession and �2.73 (SEM � 0.27), more leftward, in the 10thsession (paired t test) t(9) � 2.66, p � .05.

Group EC: Single Pointing Half Session

Adaptation. The patients’ average scores in the beginning (1to 3) trials of the pre-exposure visible condition, in the beginning(1 to 3) and in the end (43 to 45) trials of the exposure visiblecondition were 0.47° (SEM � �0.38), 7.13° (SEM � �0.64),and 1.80° (SEM � �0.37), respectively, showing adaptation. Aone-way ANOVA showed a significant difference among condi-tions, F(2, 8) � 13.05, p � .01, �p

2 � .765. Post hoc multiplecomparison revealed significant differences between the beginningand the end trials of the exposure condition ( p � .01), and betweenthe beginning trials of the pre-exposure condition and the begin-ning trials of the exposure condition ( p � .01). The differencebetween the beginning trials of the pre-exposure condition and theend trials of the exposure condition was not significant ( p � .36).

Aftereffects. The patients’ average scores in the beginning (1to 3) trials of the pre-exposure invisible condition, in the beginning(1 to 3) and in the end (13 to 15) trials of the postexposure invisiblecondition were 0.40° (SEM � �0.81), �3.00° (SEM � �1.43),and �1.40° (SEM � �1.17), respectively, showing leftward af-tereffects. A one-way ANOVA showed a significant differenceamong conditions, F(2, 8) � 6.21, p � .05, �p

2 � .608. Post hocmultiple comparisons revealed a significant difference between thebeginning trials of the pre-exposure invisible condition and thebeginning trials of the postexposure condition ( p � .05).

Patients’ Reports

All patients reported that the E treatment was more varied andless repetitive. During the C treatment, all patients spontaneouslycomplained of some minor stiffness or numbness in the right upperlimb, particularly at the end of the daily session. The examinersconsistently reported that it was generally easier to have thepatients go through the whole of the E than the C treatment.

Mediational Analyses

For these analyses, an overall cancellation score (average of thescores in the letter, bell, and star cancellation tasks), the complexdrawing scores, the sentence reading scores, and the FIM and NIHscale scores were used. The mediators were: (a) the average10-session aftereffects, (b) the average 10-session persistence ofthe aftereffects, (c) the long-term aftereffects, and (d) the average10-session adaptation effect.

A preliminary analysis by paired t tests assessed whether thepatients’ performance had improved in the week in which the Ctreatment was administered, comparing their scores before andafter this treatment: overall cancellation score, t(9) � �2.68, p �.05, complex drawing test, t(9) � �1.003, p � .34, sentencereading test, t(9) � �3.05, p � .05, NIH scale, t(9) � 2.86, p �

.05, FIM scale, t(9) � �4.71, p � .01. Accordingly, the media-tional analyses were performed on the overall cancellation, thesentence reading test, the NIH, and the FIM scale scores.

For the overall cancellation score, the effect of the aftereffectson the patients’ improvement was significant, B � .08, t(8) � 2.65,p � .05, whereas the nonmediated improvement resulted notsignificant, a � .08, t(8) � 1.19, p � .27. The mediational role ofprism exposure was replicated using the persistence of the after-effects, B � .15, t(8) � 3.12, p � .05; a � .08, t(8) � 1.35, p �.21, and the long-term aftereffects, B � .03, t(8) � �3.58, p � .01;a � �.02, t(8) � �0.54, p � .60. These results indicate a fullmediational effect (Baron & Kenny, 1986) of prism exposure, asindexed by the aftereffects, on the improvement of cancellationperformance, with larger aftereffects predicting a greater improve-ment. By contrast, no mediational effect was found for adaptation,B � .01, t(8) � 0.42, p � .69; a � �.07, t(8) � –1.14, p � .29.

For the sentence reading test, no mediational effects were found:aftereffects, B � .04, t(8) � 0.69, p � .51; a � �.06, t(8) ��0.44, p � .15, persistence of the aftereffects, B � �.06, t(8) ��0.61, p � .56; a � �.23, t(8) � �1.74, p � .12, long-termaftereffects, B � �.01, t(8) � �0.60, p � .57; a � �.18, t(8) ��2.56, p � .03, and adaptation, B � .05, t(8) � 1.44, p � .19; a ��.06, t(8) � –0.70, p � .50.

For the NIH scale no significant mediational effects were found:aftereffects, B � .01, t(8) � 0.44, p � .67; a � .08, t(8) � 1.41,p � .20, persistence of the aftereffects, B � .04, t(8) � 1.14, p �.29; a � .11, t(8) � 2.21, p � .06, long-term aftereffects, B � .01,t(8) � 1.22, p � .26; a � .08, t(8) � 2.99, p � .02, and adaptation,B � �.001, t(8) � �0.08, p � .94; a � .05, t(8) � 1.50, p � .17.

For the FIM scale, the mediational role of the aftereffectsmeasures resulted weaker than those found for the overall cancel-lation score. No mediational effect of the aftereffects was found,B � .001, t(8) � 0.47, p � .96; a � �.051, t(8) � �1.59, p � .15.The average 10-session persistence of the aftereffects mediatedweakly the FIM improvement, B � .41, t(8) � 2.22, p � .06; a ��.005, t(8) � �0.229, p � .82. Finally, the mediational effect ofthe long-term aftereffects on the FIM improvement score wassignificant, B � .010, t(8) � 2.502, p � .05, even though thenot-mediated improvement remained significant, a � �.032,t(8) � �2.64, p � .05. No mediational effect was found for theadaptation effect, B � �.002, t(8) � �0.25, p � .81; a � �.06,t(8) � –2,79, p � .02. In sum, some measures of aftereffectsexerted a significant mediational effect on the improvement of theFIM score.

Follow-Up

Seven patients were examined at Month 1, and four at the end ofthe second and third month (respectively, Assessments 8, 9, and 10).Three patients (BA, BG, and GMT) did not enter the follow-up.

Visuomotor exploratory tasks. The cancellation score (aver-age of the patients’ scores in the letter, bell, and star cancellationtasks) was used. The percentage average scores of the seven patientsat Month 1 (0.74, SD � 0.26) were comparable to those at Week 2assessments (0.67, SD � 0.25), F(1, 6) � 2.16, p � .19, �p

2 � .26.The scores of the four patients at Month 1 (0.76, SD � 0.30), Month 2(0.69, SD � 0.30), and Month 3 (0.73, SD � 0.32) assessments werealso comparable, F(2, 6) � 0.59, p � .58, �p

2 � .16.

692 FORTIS ET AL.

Functional scales. For the CBS scale, the patients’ averagescores were 2.55 (SD � 0.53) at Week 2 and 2.80 (SD � 0.33) atMonth 1 assessments (Wilcoxon’s matched pairs test, T � 0, p �.10). The scores of four patients assessed at Month 2 and Month 3did not change. In five patients the anosognosia CBS scoreswere 6.10 (SD � 5.00) at the Week 2, and 4.60 (SD � 4.20) at theMonth 1 assessment (Wilcoxon’s matched pairs test: z � 0.73, p �.46). The CBS and anosognosia scores did not change in thefollow-up. For the NIH scale, the patients’ average scoreswere 9.84 (SD � 5.34) at Week 2 and 9.84 (SD � 5.08) at Month 1assessments, F(1, 5) � 0.02, p � .87, �p

2 � .004. For the FIMscale, the patients’ average total scores were 63.58 (SD � 25.15)at Week 2 and 68.49 (SD � 29.39) at Month 1, F(1, 5) � 2.19, p �.20, �p

2 � .30. The NIH and FIM scores of the four patientsassessed at Month 2 and Month 3 did not change.

Discussion

In 10 right-brain-damaged patients a 2-week prism adaptationtreatment, combining a pointing task (Frassinetti et al., 2002), anda novel ecological task, each administered for 1 week, with acrossover design, decrease left extrapersonal visuospatial, andpersonal USN. The two treatments are equally effective in ame-liorating the different manifestations of the USN syndrome. Effect-size indexes support this conclusion. With the exception of the linebisection task, which shows no changes, the patients’ improvementin the tasks assessing USN is testified by the large effect-sizeindexes associated with time (average effect size .55, range .38 to.65). By contrast, group differences are never significant or re-markable (average effect size .16, range .003 to .33), and groups donot show a differential improvement over time (the average effectsize of the Group � Time interaction equals .20, range .11 to .27).The patients’ improvement is unrelated to baseline level of per-formance, neurological impairment, as assessed by the NIH scale,and duration of disease (see Tables 4 to 6).

Because a cross-over design was used, the data from the secondweek of treatment may be biased by a carryover effect from thefirst week, making it difficult to disentangle the specific contribu-tion of each treatment. The results, however, do not indicate acarryover effect. First, across the different tasks and indicators, thestatistical interaction between the group and time main factors isnot significant (see Tables 2 and 3), showing that the improvementof the patients’ performances is not affected by the particulartreatment in the first session (Jones & Kenward, 2003). Second, theimprovement after the first week (Bowen & Lincoln, 2007), withno differences between the two groups, indicates an equivalence ofthe treatments even before any possible carryover effect may takeplace (Grizzle, 1965). The decrease of USN during the secondweek is shown both by the ANOVAs using the three time intervals(baseline, Week 1, and Week 2) as a within-subjects main factor(see Tables 2 and 3), and by the ANCOVAs using as covariate themean scores of the three baselines (see Table 4). Taken together,these results strongly suggest that the experimental treatment is aseffective as the control one in ameliorating USN. One limitation ofthe present study is that the design did not compare the effects ofthe ecological treatment with a control group receiving no treat-ment. This comparison has been made with the classical pointingadaptation procedure (Frassinetti et al., 2002), and with prismexposure, in an early seminal study (Rossi et al., 1990).

In a recent study (Shiraishi, Yamakawa, Itou, Muraki, & Asada,2008) seven right-brain-damaged patients with a chronic left USNwore prisms displacing the field of vision rightward for 50 min perday for a period of 8 weeks, while tossing rings and performing apegboard exercise, with activities similar to those used in thisstudy. After the treatment, the patients’ eye movements showed agreater leftward deviation in visual tasks, and the center of pres-sure during standing on a force plate moved leftward and forward.These effects were observed after both the first session, and the8-week treatment, lasting for at least 6 weeks, but with no im-provement in activities of daily living. A prism adaptation treat-ment associated with a visuomotor activity may improve someaspects of the USN syndrome, but the lack of a comparison witha group of patients receiving a control treatment, and the absenceof adaptation and aftereffects measures prevent more definite con-clusions.

The present study does not show positive effects of the prismadaptation treatment on line bisection performance. Adaptationmay reduce the rightward error in line bisection (e.g., Pisella,Rode, Farne, Boisson, & Rossetti, 2002, in one out of two patients;Rossetti et al., 1998, in a group study including 16 patients).However, in a study in five patients with left USN, adaptationimproved performance in some cancellation subtests of the Behav-ioral Inattention Test (BIT, see Wilson et al., 1987), but neither inline bisection, nor in copying (Luaute et al., 2006; see also Nys, deHaan, et al., 2008, for similar evidence). In one study, two right-brain-damaged USN patients (1 and 4) showed the expected leftwardshift in line bisection after adaptation to rightward-displacing prisms,but one patient (3) exhibited a paradoxical rightward deviation (Mor-ris et al., 2004). In the present study copy drawing is improved byadaptation, in line with previous evidence (McIntosh, Rossetti, &Milner, 2002; Rossetti et al., 1998). Two prism adaptation rehabili-tation studies (Frassinetti et al., 2002; Serino et al., 2007) reported anoverall improvement of the BIT scores, without distinguishingamong the different subtests. To sum up, although prism adapta-tion has overall positive effects on the patients’ performance, asassessed by different tasks, there are differences among studies asfor the specific tasks affected by the procedure. Cancellationperformance, however, appears to be consistently improved. Fur-thermore, the lack of effects on line bisection, as well as theabsence of mediational effects of aftereffects on sentence readingperformance, suggests some specificity of the effects of prismadaptation in a rehabilitation setting.

An issue relevant to rehabilitation medicine is whether thedecrease of USN, however obtained, generalizes to a decrease indaily life disability (Bowen & Lincoln, 2007). Previous studies(Frassinetti et al., 2002; Serino et al., 2006; Serino et al., 2007),investigating the effects of prism adaptation by a pointing treat-ment for 2 weeks, measured an improvement of USN on tasksassessing the deficit itself, using psychometric tests (cancellation,reading, copying), more ecological tasks (room description, objectreaching), and the behavioral part of the BIT. Also, studies with ashorter (4 days) period of treatment used USN-specific tasks asindexes of improvement (Nys, de Haan, et al., 2008). An 8-weektreatment in chronic right-brain-damaged patients with left USNdid not detect any quantitative improvement of activities of dailyliving, as measured by the Barthel Index (Shiraishi et al., 2008).

In the present study, the improvement of the patients’ neurolog-ical impairment, as assessed by the NIH scale, is unrelated to the

693NEGLECT, PRISM EXPOSURE, AND ECOLOGICAL ACTIVITIES

effects of prism adaptation, as suggested by both the ANCOVAusing the baseline NIH score as a covariate (see Table 4), and themediational analysis. Conversely, the improvement of the patients’scores in a widely used measure of independence in everydayactivities (i.e., the FIM scale), is partly accounted for by theaftereffects, as suggested by the mediational analyses. The benefitsof a prism adaptation treatment appear to be specific to USN (i.e.,they do not extend to neurologic severity), and may possiblygeneralize to whole-person activities and independence in dailylife, as assessed in an inpatient setting. In an early seminal ran-domized study using prism exposure to rehabilitate hemianopiaand neglect (Rossi et al., 1990), 18 stroke patients who wore theprisms for 4 weeks showed an improvement of both deficits,assessed by psychometric testing, as compared with a controluntreated group of 21 patients. However, no difference was foundbetween the control and the experimental group in activitiesof daily living, assessed by the Barthel ADL mobility score(Mahoney & Barthel, 1965). This study did not report informationabout the side of the lesion and details concerning the distinctionbetween hemianopia and USN. We find it interesting that as in thepresent study, patients were engaged in everyday activities, al-though not specifically devised to enhance visuomotor adaptationand with no measures of adaptation and aftereffects being re-corded.

Given the established evidence that USN after right-hemispherestroke is associated with a more severe overall disability, andpredicts poor functional outcome (Jehkonen et al., 2006; Katz etal., 1999; Paolucci et al., 2001), the present results also indicatethat USN may contribute to these impairments, possibly togetherwith other factors (Kinsella & Ford, 1985), such as reasoning andexecutive dysfunction (Nys et al., 2005). It may be also possiblethat prism adaptation improves the FIM scores affecting arousal,which—it has long been known—is reduced after right braindamage and may be one pathological mechanism of the USNsyndrome (Heilman, Schwartz, & Watson, 1978; Robertson,2001). Recent evidence suggests however that prism adaptationdoes not affect arousal: Prism exposure does not improve overallperformance in a dichotic listening task, while reducing the right-ward bias (Jacquin-Courtois et al., 2010). Nonlateralized effects ofprism exposure on visual processing (i.e., on a local bias) are alsoon record (Bultitude, Rafal, & List, 2009).

In the pointing paradigm adopted in this study patients show theexpected (Frassinetti et al., 2002; Serino et al., 2007) adaptationand aftereffects (reviews in Redding, Rossetti, & Wallace, 2005;Redding & Wallace, 2006). At the end of the exposure period,patients exhibit adaptation, that is characterized by an overallrightward bias (see Figure 3), while the hallmark of the aftereffectsafter exposure to rightward-displacing prisms is a leftward bias(see Figure 4). The mediational analyses show that the improve-ment of USN in the cancellation tasks, and, in part, of the FIMscores is accounted for by the aftereffects (i.e., the prism-inducedleftward bias, that is opposite to the rightward bias of left USN),and not by adaptation: the larger the aftereffects, the greater theimprovement of USN. These novel findings support the effective-ness of the prism-based treatments in USN and overall disability,whatever the extent of any concurrent neurological recovery, eitherspontaneous or caused by the ongoing physiotherapy.

The role of the aftereffects emerges less sharply from a studyusing different, indirect, approaches to investigate the specific

roles of the adaptation and aftereffects (Serino et al., 2007). Pa-tients exhibiting no adaptation show little improvement in the BITand in ocular exploration, compared with patients displaying ad-aptation, with no differences related to the size of the aftereffects.However, Serino et al. (2007) split their patients’ sample into twogroups (showing/not showing adaptation, and aftereffects, arounda cut-off score based on the mean pointing error of the wholegroup): 75% of the 20 patients showed adaptation or aftereffects.In the previous study by Frassinetti et al. (2002) only one out ofseven right-brain-damaged patients (patient RD) did not showprism adaptation. RD’s improvement was confined to the conven-tional tests of the BIT (including cancellation, and copying), and tosome reading tests, but did not extend to the behavioral section ofthe BIT. The findings of Frassinetti et al. (2002) and of Serino etal. (2007) indicate that the patients’ adaptation to prisms—whichbrings about leftward aftereffects—is a necessary condition forrecovery from USN to take place. The present results furtherelucidate this issue, providing evidence that the size of the leftwardaftereffects accounts for the recovery of left USN, as assessed bycancellation tasks, and in part, for the patients’ improvement in theFIM scale. Namely, the prism-induced leftward bias, measured bythe aftereffects, is a mechanism underlying the patients’ improve-ment. These findings are in agreement with the current view thatprism adaptation reduces the ipsilesional rightward bias that char-acterizes left USN (Rode, Pisella, Rossetti, Farne, & Boisson,2003).

When should the treatment be started, and how long shouldprism adaptation be applied? The lack of relationships betweenrecovery from USN after prism adaptation and duration of diseasesuggests that the treatment should be started as soon as clinicallyfeasible. This issue may be further explored comparing the effectsof the prism adaptation treatment in chronic (i.e., with a durationof disease greater than 6 months) stroke patients versus patientswith a 1 to 2 months duration. The long-term aftereffects are moreleftward in the 10th session compared to the first session (see asimilar evidence from a single patient study in Humphreys,Watelet, & Riddoch, 2006), and the size of this leftward errormediates the patients’ improvement. Altogether, these findingsconverge to indicate that a prism-based treatment should include atleast 10 sessions. Shorter treatments lead to short-lived beneficialeffects (eight sessions, see Nys, de Haan, et al., 2008).

Results are not influenced by the presence of left hemianopia, asindexed by the comparable adaptation and aftereffects achieved byhemianopic and not hemianopic patients. A recent study (Serino etal., 2007) found that the proportion of patients with left hemi-anopia is higher in the group not showing adaptation (four out offive patients), than in the group exhibiting the effect (two out of13). These figures also indicate that one nonhemianopic patientdoes not show adaptation effects, while two hemianopic patientsdo, thus weakening the inference of a conflict between hemianopiaand adaptation. Other studies are in line with the present results.Dijkerman et al. (2003) reported adaptation and aftereffects (“in-formally” assessed) in two right-brain-damaged patients with leftUSN and hemianopia. Five right brain-damaged patients with leftUSN (three with a complete left homonymous hemianopia and twowith no visual field deficits, but visual extinction) showed leftwardaftereffects (Rossetti et al., 2004, two patients; Sarri, Kalra, Green-wood, & Driver, 2006, three patients). Similarly, Nys, de Haan etal. (2008) mentioned preserved adaptation and aftereffects in two

694 FORTIS ET AL.

right-brain-damaged patients with left USN and hemianopia. Tosum up, the compatibility between left hemianopia and aftereffectsseems the prevailing finding. This may stem from left hemianopiabeing, at least in part, an USN-related impairment (hemispatialvisual inattention: Kooistra & Heilman, 1989; Vallar, Sandroni,Rusconi, & Barbieri, 1991).

On the other hand, one study (Serino et al., 2006) suggestedsome correlation evidence that occipital damage—but not hemi-anopia—reduces prism adaptation and diminishes recovery fromUSN, as measured by the BIT. This anatomical correlation appearsto be independent of the presence of hemianopia: Five out of thenine patients with occipital damage do not show left hemianopia,that is present in two patients with lesions sparing the occipitallobe. Patient RD, who does not show adaptation, and whose lesionlargely spares the right occipital lobe, with no hemianopia, is anotable exception to this pattern. By contrast, another patient inthat series (BM) exhibits adaptation, and recovery from left USN,with a lesion extensively involving the right occipital lobe, al-though with no left hemianopia (Frassinetti et al., 2002). In thepresent series the occipital lobe is spared in all patients (see Figure1). In sum, there are indications that occipital damage, rather thanthe presence of left hemianopia, may be a relevant factor decreas-ing the patients’ prism adaptation, and recovery from USN (Serinoet al., 2006), although contrasting evidence is on record (Frassi-netti et al., 2002). A related issue concerns the neural underpin-nings of the temporary recovery from USN after successful prismadaptation: damage to the right intraparietal region, the whitematter deep to the inferior parietal lobe, and to a lesser extent, tothe white matter of the right middle frontal gyrus may prevent thedecrease of USN after prism adaptation (Sarri et al., 2008).

In conclusion, prism adaptation, achieved through a varied set ofvisuomotor “ecological” activities with the upper limbs, improvesa number of manifestations of the USN syndrome, being as effec-tive as the procedure where adaptation is achieved through re-peated pointing sessions. Second, with either treatment, improve-ments are obtained after 1 week, with a further recovery after thesecond week, making the 2-week prism adaptation treatment areliable protocol for attenuating USN. Third, the mediational anal-yses provide evidence both for positive effects of a prism adapta-tion treatment, and for an advantage of at least 10 repeated ses-sions. Fourth, both treatments not only improve the patients’ leftvisual USN, as assessed by standard psychometric tests and pre-viously reported (Frassinetti et al., 2002; Nys, de Haan, et al.,2008; Serino et al., 2007; Shiraishi et al., 2008), but also contributeto the recovery of the patients’ functional disability.

Finally, patients report a preference for the ecological activ-ities, that could be better tolerated, allowing a higher number ofparticipants with brain damage to go through the whole train-ing. Furthermore, these visuomotor activities may be easilydesigned to individual preferences and physical conditions(e.g., local orthopedic impairments). Also, home-based self-treatments may be developed, customized to the domestic en-vironment, fostering long-term maintenance of the benefits.This appears to be a specially important development, consid-ering that activities of daily living may be performed less wellin the home situation than in the hospital (Andrews & Stewart,1979; see also Young, 1994).

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Received May 14, 2009Revision received March 1, 2010

Accepted March 3, 2010 �

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