c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
Available online at www.sciencedirect.com
ScienceDirect Journal homepage: www.elsevier.com/locate/cortex
Special issue: Research report
(Un)awareness of unilateral spatial neglect: A quantitative evaluation of performance in visuo-spatial tasks Roberta Ronchi a,b,c,*, Nadia Bolognini a,b,d, Marcello Gallucci a,d, Laura Chiapella e, Lorella Algeri e, Maria Simonetta Spada e and Giuseppe Vallar a,b,d a
Department of Psychology, University of Milano-Bicocca, Milano, Italy Neuropsychological Laboratory, S. Luca Hospital, IRCCS Istituto Auxologico Italiano, Milano, Italy c Laboratory of Cognitive Neuroscience, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland d Milan Centre for Neuroscience, University of Milano-Bicocca, Piazza dell'Ateneo Nuovo 1, Milano, Italy e di Psicologia Clinica, Ospedale Papa Giovanni XXIII, Bergamo, Italy Unita b
Right-brain-damaged patients with unilateral spatial neglect are usually unaware (anosogno-
Received 23 December 2013
sic) about their spatial deficits. However, in the scientific literature there is a lack of systematic
Reviewed 6 April 2014
and quantitative evaluation of this kind of unawareness, despite the negative impact of ano-
Revised 6 June 2014
sognosia on rehabilitation programs. This study investigated anosognosia for neglect-related
Accepted 6 October 2014
impairments at different clinical tasks, by means of a quantitative assessment. Patients were tested in two different conditions (before and after execution of each task), in order to evaluate changes in the level of awareness of neglect-related behaviours triggered by task execution.
Twenty-nine right-brain-damaged patients (17 with left spatial neglect) and 27 neurologically
Unilateral left spatial neglect
unimpaired controls entered the study. Anosognosia for spatial deficits is not pervasive, with
Unawareness/anosognosia for left
different tasks evoking different degrees of awareness about neglect symptoms. Indeed, pa-
neglect and hemiplegia
tients showed a largely preserved awareness about their performance in complex visuo-motor
spatial and reading tasks; conversely, they were impaired in evaluating their spatial difficulties
Evaluation of cognitive performance
in line bisection and drawing from memory, showing over-estimation of their performance. The selectivity of the patients' unawareness of specific manifestations of spatial neglect is further supported by their preserved awareness of performance at a linguistic task, and by the absence of anosognosia for hemiplegia. This evidence indicates that discrete processes are involved in the aware monitoring of cognitive and motor performance, which can be selectively compromised by brain damage. Awareness of spatial difficulties is supported by a number of distinct components, and influenced by the specific skills required to perform a given task. © 2014 Elsevier Ltd. All rights reserved.
* Corresponding author. Laboratory of Cognitive Neuroscience, Brain Mind Institute, School of Life Sciences, Ecole Polytechnique de rale de Lausanne, Station 19, CH-1015, Lausanne, Switzerland. Fe E-mail address: [email protected]
(R. Ronchi). http://dx.doi.org/10.1016/j.cortex.2014.10.004 0010-9452/© 2014 Elsevier Ltd. All rights reserved.
c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
“Anosognosia” (from the ancient Greek, “a” without, “nosos” disease, “gnosis” knowledge) is a term, a neologism, introduced in the neurological literature by the French neurologist Joseph Babinski (Philippon & Poirier, 2009) to indicate a lack of awareness (i.e., unawareness) of a neurological deficit, specifically, left hemiplegia (Babinski, 1914; Papagno & Vallar, 2003, for revision). Indeed, the right-brain-damaged patients described by Babinski (1914) ignored or appeared to ignore their paralysis, namely they presented with anosognosia for left hemiplegia. Patients may also show indifference, lack of concern for left hemiplegia, a condition termed by Babinski anosodiaphoria (Prigatano, 2010). Here, we will use the terms of “anosognosia” and “unawareness” as synonymous, as done in the neuropsychological literature (Jenkinson, Preston, & Ellis, 2011; Langer, 2009; McGlynn & Schacter, 1989). Anosognosia is not confined to neurological deficits, namely motor, somatosensory and visual field disorders (Prigatano, 2010; Prigatano & Schacter, 1991; Vallar & Ronchi, 2006). Although the majority of studies focus on unawareness of neurological impairment (mainly motor deficits, but also somatosensory and visual half-field disorders, see Bisiach & Geminiani, 1991; Celesia, Brigell, & Vaphiades, 1997), patients may be also unaware of neuropsychological deficits, including aphasia (Kertesz, 2010; Lebrun, 1987), memory disorders (Akai, Hanyu, Sakurai, Sato, & Iwamoto, 2009), and constructional apraxia (CA) (Rinaldi, Piras, & Pizzamiglio, 2010). With respect to spatial disorders, the clinical observation of right-brain-damaged patients with left spatial neglect (Husain et al., 2001; Vallar, 1998; Vallar & Bolognini, 2014) suggests that they are not aware of their defective perception and exploration of the side of space contralateral to the side of the hemispheric lesion (contralesional). The unawareness of spatial deficits in the neglect syndrome is clinically relevant, since it impacts negatively on activities of daily living, hence on functional outcome after hospital discharge (Vossel, Weiss, Eschenbeck, & Fink, 2013). So far, only a few studies have examined anosognosia for spatial deficits in neglect experimentally. Unawareness of left neglect dyslexia (see review in Vallar, Burani, & Arduino, 2010), and of spatial neglect in davas, and Della Corte drawing was investigated by Berti, La (1996). In this seminal study, Berti et al. (1996) required rightbrain-damaged patients to perform an evaluation of their reading and drawing performances; patients were asked to report whether or not they had read correctly the sentence, and if they were happy with their drawing performance, being dichotomised as aware or unaware of left neglect dyslexia or neglect in drawing, based on their response (“yes”, “happy”), and on any subsequent confabulatory response. Berti et al. (1996) also found that anosognosia for spatial neglect in sentence reading and drawing could occur without anosognosia for left hemiplegia (Bisiach, Perani, Vallar, & Berti, 1986). A more recent study (Jehkonen, Ahonen, Dastidar, Laippala, & Vilkki, 2000) showed a double dissociation between anosognosia for left spatial neglect, assessed by asking patients to report about their spatial difficulties with a yes/no response (“Do you have any difficulties observing any part of the space?” and if necessary, giving alternatives: left, right, both,
none), and anosognosia for left hemiplegia and, more generally, for the illness. As for its neural underpinnings, unawareness of left spatial neglect, indexed by the comparison between the patients' self-rating [1 (severe) to 5 (no difficulties)] of their performance in cancellation, line bisection, drawing and text reading tasks, and that made by an external observer, was associated with lesions of the angular gyrus of the inferior parietal lobule, and the superior temporal gyrus in the right hemisphere (Vossel et al., 2012). This lesion pattern, largely overlapping with that of spatial neglect itself (review in Vallar & Bolognini, 2014), suggests a close relationship between the spatial processes dysfunctional in left neglect and their monitoring, namely the cognitive process that allow to check whether an activity or a task e here the spatial performance e is carried out correctly. Overall, the behavioural results from the literature about the presence and the extent of anosognosia for spatial neglect are not exhaustive, as previous researches have examined only selective aspects of this topic, and mostly in a qualitative way. In order to fill this gap in the literature, the present study aimed at exploring the presence of anosognosia for spatial neglect by assessing how neglect patients evaluate their ability to perform a series of different clinical tasks, commonly used for the diagnosis of spatial neglect. The rationale of using different tasks is in agreement with the concept of spatial neglect as a multi-componential syndrome (Vallar, 1998), featured by dissociable pathological neglect symptoms in different tasks (review in Vallar & Bolognini, 2014). Linear regression analyses were used to investigate how the severity of the spatial deficit in each task impacted on the monitoring of the spatial performance in that specific task. We hypothesized that neglect patients could show unawareness of the neglect-related performance deficit, independently from the specific task considered. This hypothesis is in line with a traditional, clinical, view of anosognosia as a pervasive component of left spatial neglect. Some previous evidence also supports this hypothesis. A perusal of the data by Berti and collaborators (1996) suggests the absence of double dissociation between anosognosia for neglect dyslexia and for neglect in drawing (i.e., neglect patients were either aware or unaware of both deficits); however, Berti et al. only compared two tests in a qualitative descriptive fashion, without highlighting the possible association between the level of awareness and the actual performance at each task. This information is relevant to understand whether the presence of anosognosia for spatial neglect is linked to the neglect-related behaviour: if this is the case, anosognosia for spatial neglect should selectively affect the patients' awareness of their neglect-related performance only in those tasks where a spatial deficit is present. There is also evidence, in other neuropsychological disorders, that the patients' monitoring of their cognitive performance may be more accurate after task execution (Ansell & Bucks, 2006; Barrett, Eslinger, Ballentine, & Heilman, 2005). By comparing how neglect patients evaluate their performance before and after having executed a given task, we aimed at verifying the possibility that patients showing anosognosia for neglect in a specific task before performing it, may be able (at least partially) to update their erroneous
c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
evaluation, showing improved awareness after task execution. Finally, the relationship between anosognosia for spatial neglect and anosognosia for motor deficits was explored, to verify previous evidence that monitoring processes of spatial and motor deficits are independent (Berti et al., 1996; Jehkonen et al., 2000).
Materials and methods
Twenty-nine patients (14 males, 15 females; mean age: 56.7 ± 16.4 years, range: 34e97; mean education: 11.8 ± 4.3 years; range: 5e18) with right hemisphere lesions, as assessed by CT or MRI scan, participated in this study. The aetiology of the focal lesion was vascular in 26 patients (14 ischaemic, 12 haemorrhagic; sub-acute and chronic phase, mean duration of disease: 4.5 months, range: .75e29 months), and neoplastic in three. All participants were right-handed, with no history or evidence of previous neurological or psychiatric disorders. Global cognitive efficiency was assessed using the Mini Mental State Examination (Folstein, Folstein, & Mchugh, 1975; Grigoletto, Zappala, Andeerson, & Lebowitz, 1999) or a verbal reasoning task
(Spinnler and Tognoni, 1987). Contralesional motor, somatosensory and visual half-field defects were evaluated by a standard neurological examination. Anosognosia for neurological (motor, somatosensory, visual) deficits was assessed with a short standardized interview (Bisiach, Vallar, Perani, Papagno, & Berti, 1986), comprising ad-hoc questions for each type of deficit. The score range was 0e3, with “0” corresponding to full awareness about the deficit and “3” to a severe anosognosia, unchangeable by the neurological demonstration of the deficit. The patients' demographic and neurological data are reported in Table 1. Twenty-seven right-handed neurologically unimpaired participants (13 males), matched for age (mean: 57.7 ± 15.5 years, range: 28e83) and years of education (mean: 11.6 ± 4.7 years, range: 2e18), served as controls (C).
2.2. Baseline evaluation: neuropsychological assessment for left spatial neglect The presence/absence of left spatial neglect (Nþ/N) was first assessed by a baseline evaluation, done 7 days before the experimental protocol (Day-7). The baseline assessment included the following tests: line bisection (six lines; Ronchi, Posteraro, Fortis, Bricolo, & Vallar, 2009), letter (Diller & Weinberg, 1977), star (Wilson, Cockburn, & Halligan, 1987)
Table 1 e Demographic and neurological data of 29 right-brain-damaged patients.
P1 P2 P3 P4 P5 P6 P7 P8 P9 P10 P11 P12 P13 P14 P15 P16 P17 P18 P19 P20 P21 P22 P23 P24 P25 P26 P27 P28 P29
F/75 M/74 M/36 M/40 F/65 F/34 M/46 F/41 F/52 M/34 M/53 F/50 F/66 F/38 F/37 F/34 M/70 M/71 M/54 F/57 M/61 M/54 F/97 F/73 F/50 M/60 M/77 F/74 M/72
13 12 13 8 13 13 17 8 8 13 18 17 5 13 8 12 17 18 17 8 5 13 18 5 13 8 13 8 7
I/T I/bg I/F-T-In H/F-T-P I/bg-ic I/F-T-bg I/Th-ic N/F I/bg H/bg-ic I/Sylvian region I-H/F N/F-T I/F-T-O-In-ic H/F-bg I-H/Sylvian region I/T-P-O I/Sylvian region I/bg-ic H/F-P-In-bg I/Sylvian region I/F-T-In I-H/F-P H/F-s-cort I-H/In-bg I/T-O H/bg H/F-P N/parasellar-T-bg
þ e e þ þ þ þ þ þ þ e þ þ þ þ þ þ þ þ þ e e þ þ þ e þ þ þ
e e e e e e e e e þ e e e þ þ þ e þ þ þ e e þ þ þ e e þ þ
e e e e e e e e e e þ e e þ þ þ þ þ þ e þ e þ þ þ þ e þ þ
e e e e e e e e e þSS e e e þSS-V e þSS-V e þSS þSS-V þSS e e þM-SS-V þSS-V þM-SS-V e e þSS-V þSS-V
e e e þ e e e e e e e e e e e e e e þ e e e þ þ e e e e þ
e e e e e e e e e e e e e e e e e e e e e e þ e e e e e þ
I: ischaemic lesion; H: haemorrhagic lesion; N: neoplastic lesion. F: frontal; P: parietal; T: temporal; O: occipital; In: insula; ic: internal capsule; bg: basal ganglia; Th: thalamus; s-cort: sub-cortical. M: left motor deficit; SS: left somatosensory deficit; V: left visual half-field deficit; e: left extinction to double simultaneous stimulation; AN: anosognosia; PN: personal neglect; SP: somatoparaphrenia; þ: presence of deficit; e: absence of deficit.
c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
Fig. 1 e Lesions of Nþ patients drawn on standard MRI template with a 1-mm slice distance (voxels of 1 mm3) (MRIcro software, see Rorden & Brett, 2000; www.mricro.com). Patients P13 and P29 not included, due to a neoplastic lesion (see
c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
and bell (Gauthier, Dehaut, & Joanette, 1989) cancellation tasks, sentence reading (Pizzamiglio et al., 1992), drawing tests by copy [a complex figure with five elements (Gainotti, Messerli, & Tissot, 1972), two daisies (Halligan & Marshall, 1993), one daisy (Ronchi et al., 2009), one butterfly], and from memory [a clock (Ronchi et al., 2009), one daisy, one butterfly]. Patients were classified as affected by left neglect (Nþ), if they showed a defective performance (with reference to normative data or to the controls' scores) on at least one task (between target cancellation and line bisection; Bisiach, Bulgarelli, Sterzi, & Vallar, 1983; Ferber & Karnath, 2001; Vallar & Perani, 1986). Participants who did not meet this criterion were classified as not affected by neglect (N). Accordingly, the patients' sample included 12 N (P1eP12) and 17 Nþ (P13eP29) (see below). The inspection of the scores of the N patients indicated that they did not show any sign of unilateral spatial neglect also in the other tasks (i.e., drawings and reading), not used as inclusion criteria in the present study. Following the clinical standard procedure, after each administered task, the examiner asked each patient if the task had been completed, and if the patient considered that he/she had done everything had been requested. All patients answered “yes” to the examiner's question, both when they showed signs of spatial neglect, and when they did not. Based on this clinical observation, all neglect patients could be considered “anosognosic” about their neglect-related performance in neuropsychological tasks. The lesion localisation of Nþ patients is shown in Fig. 1.
In the experimental section, both right-brain-damaged patients and healthy participants were required to evaluate their performance (see the Procedure below) relative to a list of tasks. Six tasks were chosen to assess the presence of unilateral spatial neglect, and the evaluation that patients did about their performance was taken as an indication of the presence/ absence of anosognosia for neglect-related deficits in each task. Clinically (both during the baseline and the experimental assessments) all patients with left neglect showed “anosognosia” for neglect itself, namely stated on the examiner's request that they had performed, and completed the task, according to the instructions. Accordingly, we could not compare patients based on the clinical evidence of anosognosia for neglect, since all patients were clinically “anosognosic”. We asked instead for a more quantitative, and possibly more sensitive, task-related evaluation of performance. We also asked participants for evaluating their performance in a cognitive non-spatial linguistic task, to exclude that neglect patients presented with a general impairment in evaluating their cognitive performance. Finally, we assessed the presence of motor deficits of the left (contralesional) upper limb, including tasks that require participants doing direct movements (DMs) with the arms, and executing a series of actions for which both hands were necessary or only one was sufficient (control condition for motor evaluation); also for these
motor tasks, participants had to evaluate their performance, in order to detect the presence of anosognosia for motor deficits. In detail, the tasks administered to the participants were the following:
Unilateral spatial neglect tests
- Line bisection (Ronchi et al., 2009). The task was to mark with a pencil the mid-point of six horizontal black lines (width ¼ 2 mm; length ¼ 101525 cm, two lines for each length), printed on an A4 sheet and presented in a random fixed order. The score was the deviation of the participants' mark from the objective mid-point, measured to the nearest mm; a positive score denoted a rightward displacement, a negative score a leftward displacement. - Star cancellation (modified from Wilson et al., 1987). Participants were instructed to cross out 60 small stars (30 in each side of the sheet), distributed among distracters (big stars, letters, Italian words) on an A4 sheet. - Letter cancellation (Diller & Weinberg, 1977). The task was to cross out all of 104 ‘H’ letters (53 in the left-hand side, 51 in the right-hand side of the sheet) printed on an A3 sheet, distributed among other letter distracters. - Complex drawing by copy (Fortis et al., 2010; Gainotti et al., 1972). The task was to copy a complex figure with two trees in the left-hand side, two pine trees in the right-hand side, and a house printed in the centre of an A4 sheet. - Clock drawing from memory (Ronchi et al., 2009). The task was to draw from memory the hours of a clock in a circular quadrant (Ø ¼ 12 cm), printed on an A4 sheet. - Sentence reading. Participants were given 12 sentences to read. Each sentence was printed horizontally in black uppercase letters (Arial, pt.14) in the centre of an A4 sheet and presented to participants one at a time. The length of each sentence varied from 7 to 15 words. For healthy controls, the mean bisection error was .49 mm (SD: 3.3 mm, range: 8/þ5.8); the maximum difference between omission errors on the two sides of the sheet (right-sided omissions minus left-sided omissions) was one in the Star and two in the Letter cancellation tasks (Vallar, Rusconi, Fontana, & Musicco, 1994); the maximum omission score in the complex drawing task was of .5; the maximum neglect-like errors in the clock drawing test was of 1; no neglect-like errors (Ellis, Flude, & Young, 1987) in the sentence reading task were recorded. One control participant (C4) did not perform the clock drawing test.
Cognitive non-spatial linguistic test
- Phonemic verbal fluency (Novelli et al., 1986). This task required producing as many words as they could, beginning with a given letter (F-P-L) within 60 sec for each letter; a score 16 is pathological (Novelli et al., 1986). All controls performed normal at this test (scores 16).
Table 1); patient P28 scan images not available for mapping. Maximum overlap of 14 out of 17 Nþ patients was subcortical: putamen and white matter underlying frontal, temporal and parietal regions. Montreal Neurological Institute (MNI) Zcoordinates of each transverse section are reported.
c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
Upper-limb motor tests
- Direct movements (see Bisiach, Vallar, et al., 1986). Participants were asked to raise their right and left arms, separately. - Unimanual tasks (see Marcel, Tegner, & Nimmo-Smith, 2004). Participants received instructions to perform the following actions with one hand: brush their teeth; comb their hair; drink a glass of water; open a door; sign their name. - Bimanual tasks (see Marcel et al., 2004). Participants had to perform the following actions by using both hands: shuffle a deck of cards; separate two sheets glued in the centre; tie a bow on a cylindrical box; put a key on a keychain; open a tin. Control participants executed all motor tasks in a proper way.
During the experimental session (one week after the baseline assessment, Day 1), before performing the experimental tasks (i.e., unilateral spatial neglect, cognitive non-spatial linguistic and upper-limb motor tasks; see details in the section 2.3), participants were asked to answer to the following question; for every task, we varied the description of the activity accordingly: - Pre-condition (PRE): “In your present state, how well can you perform a task in which you have to… (e.g.: cross out all the small stars on the sheet)?”. Then, the patients were asked to execute each task, and immediately at the end of each task to answer to the following question: - Post-condition (POST): “How well have you performed this task, in which you had to…?”. For the complex drawing task, scores related to left spatial neglect and CA were computed separately. CA scores were assigned to the drawings of Nþ and N patients: 2 for each element correctly oriented and drawn; 1 for each element distorted or poorly oriented, but recognizable; 0 for each element not recognizable and/or for the absence of the threedimensional component in the “house” element. Possible differences in neglect severity were removed by computing the proportion between neglect and CA scores (CAp), with the CAp scores ranging from 0 (severe CA in all drawn elements) to 1 (no CA in drawn elements). Upper-limb motor function was scored as: 0 ¼ perfect execution; 1 ¼ action performed with slowness/minimal clumsiness; 2 ¼ action performed with a great effort; 3 ¼ action impossible to perform. For each question, participants received instructions to indicate their response on a vertical 18-cm Likert scale, shown in Fig. 2a. Each scale was centred on an A4 sheet, and subdivided in 7-points graduating in colour from the bottom (dark red with a “minus” sign ¼ 1, namely: Impossible to perform) to the top (dark green with a “plus” sign ¼ 7, namely: Flawless
performance), through white at the mid-point of the scale (score ¼ 4). The examiner instructed participants to indicate, with their right index finger, the point on the scale that best represented their ability to perform each task. Therefore, in tasks poorly performed a lower score indicated awareness of the impairment, a higher score unawareness of the impairment. The experiment schedule is summarized in Fig. 2b.
The mean Likert evaluation scores of right-brain-damaged patients were compared with their performance scores obtained in each experimental task. To assess the correspondence between the patients' evaluation and their performance, linear regression analyses were conducted to assess whether the level of performance in each task (independent variable) was related to the corresponding evaluation scores. With the regressions, we examined separately both the PRE- and the POST-conditions, to verify how patients evaluated their performance in each task, before and after its execution. In the regression analyses, patients without (N) and with (Nþ) neglect were considered as a unique group, since inserting their performance scores in the model (independent variable) allows to detect the presence/absence of a pathological spatial performance in the task; this, in turn, is inherently informative about differences between N and Nþ. Figs. 3e7 show the scatterplots and regression lines of the relationship between performance and evaluation in each task: to ease the comparison between plots, performance scores were converted in T-scores, which are standardized scores. A score of 50 represents the mean (SD ± 10). A difference of 10 from the mean indicates a difference of one standard deviation: thus, a score of 60 is one standard deviation above the mean, while a score of 30 is two standard deviations below the mean. As data were not clearly fulfilling the regression assumptions, Spearman non-parametric correlation coefficients were computed on the same variables involved in the regression models, to assess the robustness of the results against possible violations of these assumptions. If parametric and non-parametric statistics bring to converging evidence (Teuber, 1955), the conclusions are statistically more reliable: indeed, the former are usually more informative and easier to interpret, the latter more robust (Siegel & Castellan, 1988). The results of the neurologically unimpaired participants were not compared statistically with those of right-braindamaged patients, as we did not expect a substantial variability in their evaluation, because there was not substantial variability in their (always good) performance. For this reason, the control group served only as a “reference” group, in order to rule out methodological flaws (i.e., lack of reliability of the tasks, or the scale, or the method) in the measurement procedure.
Evaluation of neglect-related performances
Healthy controls showed always a good performance, and a congruent positive mean evaluation before and after task
c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
Fig. 2 e A: Seven-point Likert scale used by participants to evaluate their performance, graduating in colour from dark red (task impossible to perform, score ¼ 1) to dark green (flawless performance, score ¼ 7). Before the experimental run, two practice tasks were given: during practice, participants were asked how they would evaluate losing or winning a large sum of money, by using two versions of the Likert scale, randomized between questions, namely a 7-points scale with coloured circles (shown in the figure), and a 7-points scale with coloured squares. B: Experimental schedule. In each neglect task, when the examiner posed the first (PRE) question, the test material was presented to each participant, in a central position, to facilitate the understanding of the type of task. During the PRE-condition for the cognitive non-spatial linguistic task, one verbal practice example about words starting with a specific letter (i.e., a letter different from the ones of the experimental task) was given. Evaluation of performance in the POST-condition was always required immediately after task execution. RBD: right-brain-damaged patients; C ¼ controls.
execution (PRE-condition mean scores: Line bisection ¼ 5.9, SD ¼ ±1.2; Star cancellation ¼ 6.5, SD ¼ ±.6; Complex drawing by copy ¼ 6.2, SD ¼ ±1.1; Clock drawing from memory ¼ 6.5, SD ¼ ±.6; Sentence reading ¼ 6.6, SD ¼ ±.6; Letter cancellation ¼ 6.7, SD ¼ ±.5. POST-condition mean scores: Line bisection ¼ 6.1, SD ¼ ±.8; Star cancellation ¼ 6.9, SD ¼ ±.4; Complex drawing by copy ¼ 5.9, SD ¼ ±.9; Clock drawing from memory ¼ 6.4, SD ¼ ±.9; Sentence reading ¼ 6.7, SD ¼ ±.4; Letter cancellation ¼ 6.8, SD ¼ ±.4). These findings indicate that the evaluation method was reliable, under conditions of no brain damage. In all tasks assessing spatial neglect, the evaluation scores of right-brain-damaged patients (N ¼ 29) were submitted to linear regression analyses, with task performance as the independent variable and evaluation score (in PRE- or POSTcondition) as the dependent variable. Results showed that the correspondence between performance and evaluation varied across tasks. For the cancellation tasks, the correspondence between performance and evaluation was weak before performing the task, but it became significant after the task was performed, as shown in Fig. 3. In particular, for Star cancellation (Nþ patients with defective performance: N ¼ 10), the linear
regression established that the omission percent scores were weakly associated with the patients' evaluation in the PREcondition (beta ¼ .337, F1,27 ¼ 3.45, p ¼ .074), but significantly associated with their evaluation in the POST-condition (beta ¼ .445, F1,27 ¼ 6.67, p ¼ .016). For the Letter cancellation test (Nþ patients with defective performance: N ¼ 12), no significant association was found between the two variables in the PRE-condition (beta ¼ .088, F1,27 ¼ .21, p ¼ .650), while the rate of omissions in this task predicted the evaluation scores in the POST-condition (beta ¼ .486, F1,27 ¼ 8.37, p ¼ .007). As shown in Fig. 4, performance in the Line bisection task (Nþ patients with defective performance: N ¼ 10) was unrelated to the evaluation in both the PRE- (beta ¼ .228, F1,27 ¼ 1.49, p ¼ .233), and the POST- (beta ¼ .019, F1,27 ¼ .10, p ¼ .923) conditions; similarly, performance at Clock drawing from memory (Nþ patients with defective performance: N ¼ 6) did not predict the evaluation scores in both the PRE(beta ¼ .037, F1,27 ¼ .04, p ¼ .851) and the POST- (beta ¼ .264, F1,27 ¼ 2.02, p ¼ .167) conditions. For Complex drawing by copy (Nþ patients with defective performance: N ¼ 10), we estimated the relationship between performance and evaluation while keeping constant the
c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
Fig. 3 e Scatterplots and linear regression lines of the relationship of performance in cancellation tasks [abscissa: omission errors transformed in T scores to ease comparisons between plots (mean ¼ 50, SD ¼ ±10); higher T-scores correspond to worse performance] with evaluation scores (ordinate: 1e7 Likert Scale) before (PRE), and after (POST) task execution in rightbrain-damaged patients with/without (Nþ/N) left spatial neglect.
possible intervening effects of CA. This was accomplished by adding CAp scores (see section 2.4) in the model. As shown in Fig. 5, neglect performance scores were weakly related to evaluation in the PRE-condition (beta: e.415, F2,26 ¼ 3.83, p ¼ .074), becoming however related to the patients' evaluation in the POST-condition (beta ¼ .528, F2,26 ¼ 5.45, p ¼ .020). Neglect reading errors (Fig. 5) appeared significantly associated with evaluation scores in both the PRE- (beta ¼ .483, F1,27 ¼ 8.23, p ¼ .008), and the POST- (beta ¼ .435, F1,27 ¼ 6.29, p ¼ .018) conditions (Nþ patients with defective performance: N ¼ 13). Table 2 shows a summary of the linear regression results. These findings were further corroborated by nonparametric Spearman correlation analyses, showing significant negative correlations between performance (i.e., neglect error scores) and evaluation for the same tasks in which the linear regression analyses had revealed statistically significant relationships [Star cancellation: POST-condition (r ¼ .368; p ¼ .050); Sentence reading: PRE-condition (r ¼ .526; p ¼ .003), POST-condition (r ¼ .393; p ¼ .035); Letter cancellation: POSTcondition (r ¼ .552; p ¼ .002)]. As for Complex drawing by copy, both the correlations in the PRE- (r ¼ .561; p ¼ .002), and the POST- (r ¼ .577; p ¼ .001) conditions were significant, but in this analysis the contribution of constructional disorders
was not taken into account. No other correlation proved to be significant [Line bisection: PRE-condition (r ¼ .182; p ¼ .344), POST-condition (r ¼ .112; p ¼ .564). Clock drawing from memory: PRE-condition (r ¼ .032; p ¼ .869), POST-condition (r ¼ .292; p ¼ .124)]. To sum up, in a number of clinical tasks assessing left spatial neglect, the evaluation that right-brain-damaged patients attributed to their performance was associated with the degree of their neglect-related impairment, namely: the higher was the number of spatial neglect errors, the lower was the evaluation score. This relationship was significant in the PRE-condition for the Sentence reading, with a tendency towards significance for Star cancellation and Complex drawing by copy. In the POST-condition, evaluation scores were related to performance level in Star and Letter cancellation, Complex drawing by copy, as well as in Sentence reading tasks. In the case of complex visuo-motor (cancellation and drawing) tests, the results in the POST-condition demonstrated that task execution was able to update and improve the level of awareness about neglect-related symptoms in these tasks. By contrast, the evaluation of performance in Line bisection and Clock drawing from memory tasks was never related to the spatial performance level. As shown by the regression lines of Line bisection (see Fig. 4), the lack of association between
c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
Fig. 4 e Performance in line bisection (abscissa: deviation scores from the objective mid-point transformed in T scores; higher T-scores correspond to worse performance) and clock drawing from memory (abscissa: neglect-like errors transformed in T scores; higher T-scores correspond to worse performance) tasks and evaluation (ordinate: 1e7 Likert Scale). For scatterplots, linear regression lines, and T scores, see Fig. 3
evaluation and performance is due, on average, to overestimation of the actual performance: in fact, for “good” performance, the evaluation of patients was, on average, “good”; however, as performance decreased and became “pathological”, evaluation scores, on average, did not substantially decrease.
3.2. Evaluation of performance in a non-spatial cognitive linguistic task: phonemic verbal fluency Healthy controls showed normal performance and corresponding positive evaluation (PRE-condition mean score ¼ 6, SD ¼ ±.6; POST-condition mean score ¼ 5.5, SD ¼ ±.9) in the phonemic verbal fluency task. Eleven out of 12 N participants and 7 out of 17 Nþ patients scored within the normal range in the verbal fluency test, while the remaining 11 patients (one N and 10 Nþ) had a defective performance (i.e., equivalent score ¼ 0) in this task. For right-brain-damaged patients, linear regression analyses with task performance (raw scores, i.e.: total number of correct words produced) as the independent variable and evaluation score (in PRE- or POST-condition) as the dependent variable were conducted. The patients' performance in the verbal fluency task significantly predicted evaluation scores in
both the PRE- (beta ¼ .597, F1,27 ¼ 14.96, p ¼ .001), and the POST (beta ¼ .504, F1,27 ¼ 9.20, p ¼ .005) conditions. Therefore, the more words were produced by patients, the higher were their evaluation scores. Fig. 6 shows the scatterplot of evaluation and performance scores, and Table 2 a summary of the linear regression results. Non-parametric Spearman correlation analyses confirmed a strong positive correlation between raw performance scores and evaluation ratings [PRE-condition (r ¼ .634; p < .001); POST-condition (r ¼ .547; p ¼ .002)]. To sum up, in a non-spatial linguistic task a positive association between performance and evaluation was found in right-brain-damaged patients. This pattern is clearly visible in the regression lines of Fig. 6: on average, “good” performance was associated with “good” evaluation, “pathological” performance with a decrease in evaluation scores. These results confirm that the capacity to evaluate their performance in a cognitive task, not requiring spatial abilities, was not compromised in neglect patients.
Evaluation of upper-limb motor performances
In the control group, the performance score was constant for DM and unimanual (UNIM) actions, with all controls obtaining
c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
Fig. 5 e Performance in reading (abscissa: neglect-type errors transformed in T scores; higher T-scores correspond to worse performance) and complex drawing by copy (abscissa: neglect omission errors transformed in T scores; higher T-scores correspond to worse performance) tasks and evaluation (ordinate: 1e7 Likert Scale). For scatterplots, linear regression lines, and T scores, see Fig. 3.
Fig. 6 e Performance in phonemic verbal fluency (abscissa: number of produced words transformed in T scores; higher T-scores correspond to better performance) and evaluation (ordinate: 1e7 Likert Scale). Dþ/D¡: patients with defective (equivalent score ¼ 0)/preserved performance. For scatterplots, linear regression lines, and T scores, see Fig. 3.
c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
Fig. 7 e Performance in the motor direct movement and bimanual tasks (abscissa: error scores transformed in T scores; higher T-scores correspond to worse performance) and evaluation (ordinate: 1e7 Likert Scale) before (PRE) and after (POST) task execution in right-brain-damaged patients, with and without (Nþ and N¡) left unilateral spatial neglect. For scatterplots, linear regression lines, and T scores, see Fig. 3.
the maximum score of 0 (perfect execution). The bimanual tasks (BIM) were well performed (scores between 0 and 1); only one control participant (C27) scored 2 in one BIM; this item was not considered. Controls attributed themselves coherent positive evaluation scores (PRE-condition mean scores: DM ¼ 7, SD ¼ ±.1; UNIM ¼ 7, SD ¼ ±.1; BIM ¼ 6.7, SD ¼ ±.3. POST-condition mean scores: DM ¼ 7, SD ¼ ±.1; UNIM ¼ 7, SD ¼ ±.1; BIM ¼ 6.8, SD ¼ ±.3). A series of linear regression analyses with motor performance as the independent variable (score range: 0e3) and evaluation score (in PRE- or POST-condition) as the dependent variable were conducted in 28 out of the 29 right-braindamaged patients (one patient was not available for the evaluation of motor functions). In patients, performance in unimanual tasks was constant and flawless (all scores ¼ 0, perfect execution): therefore, no further analyses were conducted. Linear regression analyses showed that performance in motor tasks, when a DM or BIM action was required, predicted the evaluation scores both in the PRE-condition [DM: (beta ¼ .878, F1,26 ¼ 87.35, p < .001); BIM: (beta ¼ .726, F1,26 ¼ 29.02, p < .001)] and in the POST-condition [DM: (beta ¼ .653, F1,26 ¼ 19.31, p < .001); BIM: (beta ¼ .733, F1,26 ¼ 30.27, p < .001)]. Therefore, the higher was the performance score (i.e., poor motor performance, see section 2.4), the lower was the patients' evaluation, both before and after
task execution. Fig. 7 shows the scatterplot of the patients' evaluation and performance scores (DM and BIM), and Table 2 a summary of the linear regression results. Non-parametric Spearman correlations confirmed a negative correlation between performance and evaluation scores [DM: PRE-condition (r ¼ .910; p < .001), POST-condition (r ¼ .754; p < .001); BIM: PRE-condition (r ¼ .617; p < .001), POST-condition (r ¼ .738; p < .001)]. Overall, right-brain-damaged patients, as a group, were aware about their motor impairments, attributing themselves, on average, low scores in the medium/negative part of the Likert scale for the motor actions that they were unable to perform (i.e., higher performance error scores). Conversely, in the evaluation of cognitive performance (see sections 3.1 and 3.2) patients scored, on average, in the green upper part of the Likert scale. Finally, we also examined the evaluation ratings of the two right-brain-damaged patients who presented anosognosia for hemiplegia in the baseline evaluation (P23 and P25; see Table 1). Although the two (clinical and experimental) assessments were different, it may be of interest to illustrate qualitatively the specific experimental response patterns of these patients. During the baseline assessment, P25 showed a mild anosognosia for hemiplegia (score ¼ 1/3), becoming aware of the motor impairment only after a specific question about the left
c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
Table 2 e Linear regression analyses made on the evaluation score (dependent variable) and the level of performance (independent variable) at spatial neglect, non-spatial (linguistic), and motor tasks. The sample of neurological patients is considered (N ¼ 29 for spatial and linguistic tests; N ¼ 28 for motor tests). For spatial neglect tests and motor tasks, the erroneous performance is considered (greater the score, worst the performance); for the non-spatial linguistic task, the accuracy performance is considered (greater the score, better the performance). Beta value PRE-evaluation Unilateral spatial neglect tests Star cancellation Letter Cancellation Line bisection Clock drawing from memory Complex drawing by copy Reading Non-spatial linguistic task Phonemic verbal fluency Upper-limb motor tasks Direct movement Unimanual Bimanual
.337 .088 .228 .037
.445a .486a .019 .264
.878a n.a. .726a
.653a n.a. .733a
Statistically significant regression; n.a. ¼ not assessed as performance was constant (all scores ¼ 0, perfect execution). The same results were found excluding the two chronic patients (one N and one Nþ) from the patients' group.
upper limbs (Bisiach, Vallar, et al., 1986); P23 presented with a severe anosognosia for hemiplegia (score: 3/3), as she was not able to acknowledge the motor deficit also after the neurological demonstration by the examiner. In the experimental assessment, P25 evaluated negatively her performance in DM of the left arm (score PRE-condition: 2; score POST-condition: 3), and BIM actions (mean score PRE-condition: 2.6; mean score POST-condition: 2.4), coherently with her failure in the execution of the motor tasks. With respect to P23, when asked to raise the left arm (DM), which was an action for her impossible to perform, P23 evaluated this task with a medium/ positive score in the PRE-condition (score: 4), but she was aware about her defective performance immediately after task execution (score POST-condition: 1); however, she demonstrated poor awareness about task performance in BIM actions (mean score PRE-condition: 5.2; mean score POSTcondition: 4.4), even if she was completely unable to perform the required actions.
The main findings of this study, investigating quantitatively anosognosia for left spatial neglect (Berti et al., 1996; Jehkonen et al., 2000; Vossel et al., 2013), may be summarized as follows: 1) for some, but not all, tasks assessing spatial neglect, the patients' evaluation of performance is related to the level of spatial impairment in that specific task, suggesting that some
tasks may elicit more awareness of the pathological spatial performance; 2) task execution improves the accuracy of the patients' evaluation of performance; 3) the patients' ability to correctly evaluate performance in other domains (linguistic and motor) is preserved. All neglect patients exhibited “anosognosia” for spatial neglect at the clinical level, namely: when directly inquired, they stated to have completed and accurately performed each task assessing the presence of spatial neglect. Accordingly, we did not compare patients based on the clinical evidence of anosognosia, asking instead for a quantitative and more sensitive task-specific evaluation. Based on this approach, right-brain-damaged patients present with relatively preserved ability in evaluating their level of performance in Cancellation, Sentence reading, and Complex drawing by copy tasks. Conversely, they are impaired in correctly evaluating their level of performance in Line bisection, a perceptual visuo-motor task, and in Clock drawing from memory, a task assessing representational neglect (Beschin, Cocchini, Della Sala, & Logie, 1997; Lepore, Conson, Ferrigno, Grossi, & Trojano, 2004), showing anosognosia for neglect-related symptoms at these tasks. Together with the absence of monitoring deficits in linguistic (non-spatial) and motor tasks, the presence of anosognosia for some, but not all, neglectrelated deficits suggests a task-specific account of anosognosia for spatial neglect. This result disproves the initial hypothesis of a pervasive presence of anosognosia for all manifestations of neglect. By adopting, for the first time, a quantitative and complete assessment of neglect performance at different tasks, which involve different spatial abilities, and by analysing the relationship between the patients' evaluation and their actual performance at each task, we demonstrate that not all clinical tests are able to elicit the same degree of awareness of neglect performance. The finding of significant regression coefficients in some tasks, but not in others, suggests that the different tasks assessing spatial neglect used in this study evoke different level of awareness, although they were not directly compared in this respect. Hence, in line with the widely accepted view that neglect is a multi-componential syndrome (Vallar & Bolognini, 2014), also anosognosia for neglect appears to be modular in nature, and, therefore, dissociable across tasks assessing different aspects of the syndrome. However, at least for line bisection, another interpretation of the defective evaluation of performance should be considered, related to possible differences in task difficulty (Vallar, 2000). In this view, the bisection task might be “easier”, hence requiring less engagement of cognitive resources, such as executive function and spatial working memory (Husain et al., 2001; Malhotra et al., 2005), as compared with cancellation and copy drawing tasks. However, it is noteworthy that left spatial neglect may selectively affect the patients' performance in cancellation and bisection tasks: right-braindamaged patients may indeed show left neglect in cancellation, but not in bisection, tasks, and vice-versa (Ferber & Karnath, 2001; Halligan & Marshall, 1992; Marshall & Halligan, 1995; Vallar & Bolognini, 2014), conjuring up a double dissociation of deficits (Teuber, 1955; Vallar, 2000). Furthermore, these two tasks have different neural underpinnings (Baier, Mueller, Fechir, & Dieterich, 2010; Daini,
c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
Angelelli, Antonucci, Cappa, & Vallar, 2002; Revill, Karnath, & Rorden, 2011; Rorden, Fruhmann Berger, & Karnath, 2006; Verdon, Schwartz, Lovblad, Hauert, & Vuilleumier, 2010). As for spatial working and short-term memory there is evidence that some patients with left neglect do not show such deficits (Ronchi et al., 2009) and, vice-versa, i.e., right-brain-damaged patients with defective spatial short-term memory do not exhibit left neglect (De Renzi & Nichelli, 1975). The existence of both behavioural and neural double dissociations argues against an explanation based on a mere difference in task difficulty of cancellation versus bisection tasks, inducing different levels of awareness of the spatial abilities. Rather, it points to a task-specific account of anosognosia for left spatial neglect. Furthermore, any other difference in the patients' evaluation that can be attributed to a “subjective” perception of task difficulty, independently from the presence of spatial neglect, has been taken into account and removed by the inclusion of patients without neglect symptoms in the regression analyses. With respect to the tests eliciting a greater degree of awareness of the spatial deficit, Sentence reading, Complex drawing by copy and Cancellation tasks trigger patients' awareness. As for reading, patients show a relative accurate prediction of their performance before the task, and their evaluation is accurate after task execution. Previous observations, based on a dichotomous classificatory approach, indicate that some patients are unaware of neglect dyslexia (Berti et al., 1996). By contrast, in our study, in which a direct comparison between task's performance and evaluation is done, overall, right-brain-damaged patients appear to be able to monitor their neglect-related reading symptoms. Nevertheless, inspection of Fig. 5 shows that three patients evaluate their performance in the POST-condition with the maximum evaluation score (i.e., score ¼ 7, subjective flawless performance), in spite of a very severe neglect dyslexia (i.e., number of neglect reading errors greater than 10 out of 12), therefore showing anosognosia for the neglect-related reading deficit. Thus, although anosognosia for neglect dyslexia can be observed in the individual patient, we find an average trend of accuracy in monitoring the neglect-related performance. It may be also noticed that reading involves stimuli made up by multiple components, with variable contributions from phonological, lexical, and semantic systems [i.e., sequences of letters, that may constitute a word, meaningless or not, though pronounceable (a nonword); see Vallar et al., 2010]. Seen in this perspective, written letter strings share some features with the multiple-component stimuli used in target cancellation and drawing tasks; reading has also a motor (eye movement) component. Neglect performance in tasks requiring complex visuomotor abilities and serial exploration, such as copy of a drawing and target cancellation tests, are better monitored by patients and their evaluation of performance is relatively coherent with the actual task execution. For the Complex drawing by copy, moreover, the influence of neglect errors on the patients' evaluation survives also when the contribution of CA (Gainotti & Tiacci, 1970; Gainotti, 1985; Hier, Mondlock, & Caplan, 1983a, 1983b; Kleist, 1934; Russell et al., 2010) is partialled out.
All together, the present findings indicate that anosognosia for neglect-related behaviours may be selective, affecting only specific manifestations of unilateral spatial neglect. As neglect performance may be dissociated in line bisection and cancellation tests (Halligan & Marshall, 1992; Marshall & Halligan, 1995), in the same way the patients' awareness about performance in these two tasks can dissociate. This specific “neglect of neglect” (a term which we would suggest here) is in line with the view that the monitoring systems of spatial functions can be highly multi-componential. Furthermore, within left spatial neglect, complex visuo-motor (cancellation and copy drawing) and sentence reading tasks appear to be able to elicit the greater level of awareness of spatial deficit. In agreement with our initial hypothesis, we found that the evaluation of patients about their level of performance in spatial tasks is adjustable by task execution. This conclusion is suggested by different statistical results found when performance levels were compared with evaluations made before (PRE-) or after (POST-) task execution. This did not occur systematically, but selectively for a subset of the tasks considered, namely: target cancellation, and copy of a drawing. Conversely, task execution is unable to update (and improve) the patients' evaluation of their performance at the Line bisection and Clock drawing from memory tasks. Even if cancellation, drawing and bisection are all visuo-motor tests, the visuo-motor feedback about the pathological neglectrelated performance seems more “salient” in target cancellation and in drawing by copy, than that in Line bisection. Moreover, cancellation and drawing tasks require a serial exploration and continuous on-line inspection of the performance, which is absent in line bisection. This evidence could account for the difference in the role of task execution in improving the level of awareness across different tests. The possibility may be entertained that the patients' evaluation of performance prior to task execution could have been influenced by a generic knowledge about their abilities, stored in memory representations in the pre-morbid condition. Conversely, failure to perform the task may elicit an update of their actual abilities, leading to a more accurate judgment after execution (for related evidence about anosognosia for hemiplegia see: Berti et al., 1996; Cocchini, Beschin, & Della Sala, 2002; Marcel et al., 2004). Notably, patients had already performed all experimental visuo-spatial tests in the baseline assessment, but evaluation of performance was not required. In line with these conclusions, patients with probable Alzheimer disease may show a pre-test over-estimation of visuospatial abilities, which is reduced in the post-testing stage, at variance with their evaluation of memory, for which the pattern shown by patients is opposite, with anosognosia emerging in the post-test (Barrett et al., 2005). There is also evidence, however, that patients with probable Alzheimer disease in an early stage are more aware of their memory competences after exposure to a memory task (Ansell & Bucks, 2006). The pattern of results in the cognitive spatial versus nonspatial tasks' evaluation further suggests that anosognosia for left spatial neglect, when present, is a specific deficit in spatial performance monitoring. In fact, right-brain-damaged patients correctly estimate their competences in the control
c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
(not assessing visuo-spatial abilities) verbal fluency test: neglect patients with a pathological verbal fluency score evaluate worst their performance, both before and after task execution. Finally, right-brain-damaged patients are aware of their motor abilities, regardless of the presence of left spatial neglect: when they are unable to perform the motor tasks, their evaluations are strongly negative, in line with their actual level of performance. As a group, patients show awareness of motor deficits in both direct questions and BIM. Patients' awareness of their motor inabilities may be triggered by repeated failure on motor tasks, particularly during physical rehabilitation. There is also evidence, however, that awareness for motor deficits may vary in relation to the specific evaluation test (Cocchini, Beschin, Fotopoulou, & Della Sala, 2010; Marcel et al., 2004; NimmoSmith, Marcel, & Tegner, 2005; Orfei et al., 2007; Starkstein, Jorge, & Robinson, 2010). A perusal of our patients' sample indicates that in the baseline assessment one patient (P23) presented with a severe anosognosia for hemiplegia, as evaluated with a standard clinical score (Bisiach, Vallar, et al., 1986). Notwithstanding the tasks administered during the experimental protocol are different, possibly prompting different results, P23's evaluation scores in DM and BIM are indicative of unawareness of motor deficits, with the evaluation scores in the medium/positive part of the Likert scale. The only negative score this patient attributed to herself, coherent with the failure in raising the left arm, was just after task execution, with motor performance triggering a short-term modulation of awareness of the motor defect. In the same patient, the negative feedback provided by failed motor performance was not effective for BIM, but only for DM request, indicating differences is sensitivity between the two tasks for eliciting awareness of hemiplegia (Marcel et al., 2004). Indeed, as first found in a seminal group study (Bisiach, Vallar, et al., 1986), unilateral spatial neglect and anosognosia for left motor deficits following right-hemisphere damage may occur independently of each other (Appelros, Karlsson, & Hennerdal, 2007; Berti et al., 2005; Bottini, Bisiach, Sterzi, & Vallar, 2002; Kortte & Hillis, 2009; Rode et al., 1992; Rode, Perenin, Honore, & Boisson, 1998; Starkstein, Fedoroff, Price, & Robinson, 1993). Our findings provide evidence that also anosognosia for left spatial neglect and anosognosia for left hemiplegia are independent deficits (see also Jehkonen et al., 2000). To summarize, the existence of anosognosia for neglectrelated performance confined to specific tasks supports the view that the monitoring systems for spatial competences are discrete, and may be selectively damaged, in line with previous evidence across different domains (Barrett et al., 2005; Leicht, Berwig & Gertz, 2010; Marcel et al., 2004; Nielsen, 1938; Spinazzola, Pia, Folegatti, Marchetti, & Berti, 2008; Von Hagen & Ives, 1937). When anosognosia for neglect symptoms is detected, the patients' evaluation of their spatial performance cannot be traced back to a non-specific effect of brain damage (as shown by the accurate evaluation of rightbrain-damaged patients without neglect), or to a general compromised capacity to evaluate a cognitive performance (as shown by the patients' evaluation of performance in the
verbal fluency test). Finally, the features of the tasks and stimuli are able to elicit and modulate the level of awareness of the defective performance: neglect patients are indeed more aware of their neglect-related symptoms in the sentence reading test, independently from the feedback provided by the failure to execute the task. On the other hand, the feedback about a pathological spatial performance elicited by task execution is able to induce a more accurate awareness of the spatial deficits, but only in cancellation and drawing by copy tasks. These conclusions are based on statistically significant versus non-significant correspondences between evaluation and performance in these tests, rather than on the statistical comparison between pre-versus post-evaluation ratings of performance, and among tests. To summarise, awareness of neglect-related behaviours occurs mainly in reading and visuo-motor spatial tests, involving multiple-component stimuli (e.g., multiple targets, letter strings, drawings), and serial exploration.
Acknowledgements The work was supported in part by the ‘Fondo di Ateneo’ grant, from the University of Milano-Bicocca to G.V. and N.B., and the Ricerca Corrente from the IRCCS Istituto Auxologico Italiano, Milano.
Akai, T., Hanyu, H., Sakurai, H., Sato, T., & Iwamoto, T. (2009). Longitudinal patterns of unawareness of memory deficits in mild Alzheimer's disease. Geriatrics and Gerontology International, 9(1), 16e20. Ansell, E. L., & Bucks, R. S. (2006). Mnemonic anosognosia in Alzheimer's disease: a test of Agnew and Morris (1998). Neuropsychologia, 44(7), 1095e1102. Appelros, P., Karlsson, G. M., & Hennerdal, S. (2007). Anosognosia versus unilateral neglect. Coexistence and their relations to age, stroke severity, lesion site and cognition. European Journal of Neurology, 14(1), 54e59. l’e tude des troubles mentaux Babinski, J. (1914). Contribution a miple gie organique cerebrale (anosognosie). Revue dans l’he Neurologique, 27, 845e848. Baier, B., Mueller, N., Fechir, M., & Dieterich, M. (2010). Line bisection error and its anatomic correlate. Stroke, 41(7), 1561e1563. Barrett, A., Eslinger, P. J., Ballentine, N. H., & Heilman, K. M. (2005). Unawareness of cognitive deficit (cognitive anosognosia) in probable ad and control subjects. Neurology, 64(4), 693e699. Berti, A., Bottini, G., Gandola, M., Pia, L., Smania, N., Stracciari, A., et al. (2005). Shared cortical anatomy for motor awareness and motor control. Science, 309(5733), 488e491. davas, E., & Della Corte, M. (1996). Anosognosia for Berti, A., La hemiplegia, neglect dyslexia, and drawing neglect: clinical findings and theoretical considerations. Journal of the International Neuropsychological Society, 2(5), 426e440. Beschin, N., Cocchini, G., Della Sala, S., & Logie, R. H. (1997). What the eyes perceive, the brain ignores: a case of pure unilateral representational neglect. Cortex, 33(1), 3e26. Bisiach, E., Bulgarelli, C., Sterzi, R., & Vallar, G. (1983). Line bisection and cognitive plasticity of unilateral neglect of space. Brain and Cognition, 2(1), 32e38.
c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
Bisiach, E., & Geminiani, G. (1991). Anosognosia related to hemiplegia and hemianopia. In G. P. Prigatano, & D. L. Schacter (Eds.), Awareness of deficit after brain injury (pp. 17e39). New York: Oxford University Press. Bisiach, E., Perani, D., Vallar, G., & Berti, A. (1986a). Unilateral neglect: personal and extrapersonal. Neuropsychologia, 24(6), 759e767. Bisiach, E., Vallar, G., Perani, D., Papagno, C., & Berti, A. (1986b). Unawareness of disease following lesions of the right hemisphere: anosognosia for hemiplegia and anosognosia for hemianopia. Neuropsychologia, 24(4), 471e482. Bottini, G., Bisiach, E., Sterzi, R., & Vallar, G. (2002). Feeling touches in someone else's hand. NeuroReport, 13(2), 249e252. Celesia, G. G., Brigell, M. G., & Vaphiades, M. S. (1997). Hemianopic anosognosia. Neurology, 49(1), 88e97. Cocchini, G., Beschin, N., & Della Sala, S. (2002). Chronic anosognosia: a case report and theoretical account. Neuropsychologia, 40(12), 2030e2038. Cocchini, G., Beschin, N., Fotopoulou, A., & Della Sala, S. (2010). Explicit and implicit anosognosia or upper limb motor impairment. Neuropsychologia, 48(5), 1489e1494. Daini, R., Angelelli, P., Antonucci, G., Cappa, S. E., & Vallar, G. (2002). Exploring the syndrome of spatial unilateral neglect through an illusion of length. Experimental Brain Research, 144(2), 224e237. De Renzi, E., & Nichelli, P. (1975). Verbal and non-verbal shortterm memory impairment following hemispheric damage. Cortex, 11(4), 341e354. Diller, L., & Weinberg, J. (1977). Hemi-Inattention in rehabilitation. The evolution of a rational remediation program. In E. A. Weinstein, & R. P. Friedland (Eds.), Hemi-inattention and hemisphere specialization (pp. 62e82). New York: Raven Press. Ellis, A. W., Flude, B. M., & Young, A. W. (1987). “Neglect dyslexia” and the early visual processing of letters in words and nonwords. Cognitive Neuropsychology, 4(4), 439e464. Ferber, S., & Karnath, H. O. (2001). How to assess spatial neglecteline bisection or cancellation tasks? Journal of Clinical and Experimental Neuropsychology, 23(5), 599e607. Folstein, M., Folstein, S. E., & Mchugh, P. R. (1975). “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189e198. Fortis, P., Maravita, A., Gallucci, M., Ronchi, R., Grassi, E., Senna, I., et al. (2010). Rehabilitating patients with left spatial neglect by prism exposure during a visuomotor activity. Neuropsychology, 24(6), 681e697. Gainotti, G. (1985). Constructional apraxia. In J. A. M. Frederiks, G. W. Bruyn, & H. L. Klawans (Eds.), Clinical neuropsychology (Vol. 1(45), pp. 491e506). Amsterdam: Elsevier Science Publishers, B.V. Gainotti, G., Messerli, P., & Tissot, R. (1972). Qualitative analysis of unilateral spatial neglect in relation to laterality of cerebral lesions. Journal of Neurology Neurosurgery and Psychiatry, 35(4), 545e550. Gainotti, G., & Tiacci, C. (1970). Patterns of drawing disability in right and left hemispheric patients. Neuropsychologia, 8(3), 379e384. Gauthier, L., Dehaut, F., & Joanette, Y. (1989). The Bells Test: a quantitative and qualitative test for visual neglect. International Journal of Clinical Neuropsychology, 11(2), 49e54. Grigoletto, F., Zappala, G., Andeerson, D. W., & Lebowitz, B. D. (1999). Norms for the mini-mental state examination in a healthy population. Neurology, 53(2), 315e320. Halligan, P. W., & Marshall, J. C. (1992). Left visuo-spatial neglect: a meaningless entity? Cortex, 28(4), 525e535. Halligan, P. W., & Marshall, J. C. (1993). When two is one: a case study of spatial parsing in visual neglect. Perception, 22(3), 309e312.
Hier, D. B., Mondlock, J., & Caplan, L. R. (1983a). Recovery of behavioral abnormalities after right hemisphere stroke. Neurology, 33(3), 345e350. Hier, D. B., Mondlock, J., & Caplan, L. R. (1983b). Behavioral abnormalities after right hemisphere stroke. Neurology, 33(3), 337e344. Husain, M., Mannan, S., Hodgson, T., Wojciulik, E., Driver, J., & Kennard, C. (2001). Impaired spatial working memory across saccades contributes to abnormal search in parietal neglect. Brain, 124(5), 941e952. Jehkonen, M., Ahonen, J. P., Dastidar, P., Laippala, P., & Vilkki, J. (2000). Unawareness of deficits after right hemisphere stroke: double-dissociations of anosognosias. Acta Neurologica Scandinavica, 102(6), 378e384. Jenkinson, P. M., Preston, C., & Ellis, S. J. (2011). Unawareness after stroke: a review and practical guide to understanding, assessing, and managing anosognosia for hemiplegia. Journal of Clinical and Experimental Neuropsychology, 33(10), 1079e1093. Kertesz, A. (2010). Anosognosia for aphasia. In G. P. Prigatano (Ed.), The study of anosognosia (pp. 113e122). Oxford: Oxford University Press. Kleist, K. (1934). Gehirnpathologie. Leipzig: J. A. Barth. Kortte, K., & Hillis, A. E. (2009). Recent advances in the understanding of neglect and anosognosia following right hemisphere stroke. Current Neurology and Neuroscience Reports, 9(6), 459e465. Langer, K. G. (2009). Babinski's anosognosia for hemiplegia in early twentieth-century French neurology. Journal of the History of Neurosciences, 18(4), 387e405. Lebrun, Y. (1987). Anosognosia in aphasics. Cortex, 23(2), 251e263. Leicht, H., Berwig, M., & Gertz, H. J. (2010). Anosognosia in Alzheimer's disease: the role of impairment levels in assessment of insight across domains. Journal of the International Neuropsychological Society, 16(3), 463e473. Lepore, M., Conson, M., Ferrigno, A., Grossi, D., & Trojano, L. (2004). Spatial transpositions across tasks and response modalities: exploring representational allochiria. Neurocase, 10(5), 386e392. € ger, H. R., Parton, A., Greenwood, R., Playford, E. D., Malhotra, P., Ja Brown, M. M., et al. (2005). Spatial working memory capacity in unilateral neglect. Brain, 128(2), 424e435. Marcel, A. J., Tegner, R., & Nimmo-Smith, I. (2004). Anosognosia for plegia: specificity, extension, partiality and disunity of bodily unawareness. Cortex, 40(1), 19e40. Marshall, J. C., & Halligan, P. W. (1995). Within- and between-task dissociations in visuo-spatial neglect: a case study. Cortex, 31(2), 367e376. McGlynn, S. M., & Schacter, D. L. (1989). Unawareness of deficits in neuropsychological syndromes. Journal of Clinical and Experimental Neuropsychology, 11(2), 143e205. Nielsen, J. M. (1938). Gerstmann syndrome: finger agnosia, agraphia, confusion of right and left and acalculia. Archives of Neurology and Psychiatry, 39(3), 536e559. Nimmo-Smith, I., Marcel, A. J., & Tegner, R. (2005). A diagnostic test of unawareness of bilateral motor task abilities in anosognosia for hemiplegia. Journal of Neurology Neurosurgery and Psychiatry, 76(8), 1167e1169. Novelli, G., Papagno, C., Capitani, E., Laiacona, M., Vallar, G., & Cappa, S. F. (1986). Tre test clinici di ricerca e produzione lessicale. Taratura su soggetti normali. Archivio di Psicologia Neurologia e Psichiatria, 47(4), 477e506. Orfei, M. D., Robinson, R. G., Prigatano, G. P., Starkstein, S., Ru¨sch, N., Bria, P., et al. (2007). Anosognosia for hemiplegia after stroke is a multifaceted phenomenon: a systematic review of the literature. Brain, 130(12), 3075e3090. Papagno, C., & Vallar, G. (2003). Anosognosia for left hemiplegia: Babinski's (1914) cases. In C. Code, C.-W. Wallesch, Y. Joanette,
c o r t e x 6 1 ( 2 0 1 4 ) 1 6 7 e1 8 2
& A. R. Lecours (Eds.), Vol. 2s. Classic cases in neuropsychology (pp. 171e189). Hove, East Sussex: Psychology Press. Philippon, J., & Poirier, J. (2009). Joseph Babinski. A biography. Oxford, England: Oxford University Press. Pizzamiglio, L., Antonucci, G., Judica, A., Montenero, P., Razzano, C., & Zoccolotti, P. (1992). Cognitive rehabilitation of the hemineglect disorder in chronic patients with unilateral brain damage. Journal of Clinical and Experimental Neuropsychology, 14(6), 901e923. Prigatano, G. P. (Ed.). (2010). The study of anosognosia. Oxford: Oxford University Press. Prigatano, G. P., & Schacter, D. L. (Eds.). (1991). Awareness of deficit after brain injury. Clinical and theoretical issues. Oxford: Oxford University Press. Revill, K. P., Karnath, H. O., & Rorden, C. (2011). Distinct anatomy for visual search and bisection: a neuroimaging study. NeuroImage, 57(2), 476e481. Rinaldi, M. C., Piras, F., & Pizzamiglio, L. (2010). Lack of awareness for spatial and verbal constructive apraxia. Neuropsychologia, 48(6), 1574e1582. Rode, G., Charles, N., Perenin, M. T., Vighetto, A., Trillet, M., & Aimard, G. (1992). Partial remission of hemiplegia and somatoparaphrenia through vestibular stimulation in a case of unilateral neglect. Cortex, 28(2), 203e208. Rode, G., Perenin, M. T., Honore, J., & Boisson, D. (1998). Improvement of the motor deficit of neglect patients through vestibular stimulation: evidence for a motor neglect component. Cortex, 34(2), 253e261. Ronchi, R., Posteraro, L., Fortis, F., Bricolo, E., & Vallar, G. (2009). Perseveration in left spatial neglect: drawing and cancellation tasks. Cortex, 45(3), 300e312. Rorden, C., & Brett, M. (2000). Stereotaxic display of brain lesions. Behavioural Neurology, 12(4), 191e200. Rorden, C., Fruhmann Berger, M., & Karnath, H. O. (2006). Disturbed line bisection is associated with posterior brain lesions. Brain Research, 1080(1), 17e25. Russell, C., Deidda, C., Malhotra, P., Crinion, J. T., Merola, S., & Husain, M. (2010). A deficit of spatial remapping in constructional apraxia after right-hemisphere stroke. Brain, 133(4), 1239e1251. Siegel, S., & Castellan, N. J. (1988). Nonparametric statistics for the behavioral sciences. New York: McGraw-Hill. Spinazzola, L., Pia, L., Folegatti, A., Marchetti, C., & Berti, A. (2008). Modular structure of awareness for sensorimotor disorders: evidence from anosognosia for hemiplegia and anosognosia for hemianaesthesia. Neuropsychologia, 46(3), 915e926. Spinnler, H., & Tognoni, G. (1987). Standardizzazione e taratura italiana di test neuropsicologici. The Italian Journal of Neurological Sciences, 6(Suppl. 8), 1e120.
Starkstein, S. E., Fedoroff, J. P., Price, T. R., & Robinson, R. G. (1993). Denial of illness scale: a reliability and validity study. Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 6(2), 93e97. Starkstein, S. E., Jorge, R. E., & Robinson, R. G. (2010). The frequency, clinical correlates, and mechanism of anosognosia after stroke. The Canadian Journal of Psychiatry, 55(6), 355e361. Teuber, H.-L. (1955). Physiological psychology. Annual Review of Psychology, 6, 267e296. Vallar, G. (1998). Spatial hemineglect in humans. Trends in Cognitive Sciences, 2(3), 87e97. Vallar, G. (2000). The methodological foundations of human neuropsychology: studies in brain-damaged patients. In F. Boller, J. Grafman, & G. Rizzolatti (Eds.), Handbook of neuropsychology (Vol. 1, pp. 305e344). Amsterdam, The Netherlands: Elsevier. Vallar, G., & Bolognini, N. (2014). Unilateral spatial neglect. In A. C. Nobre, & S. Kastner (Eds.), Oxford handbook of attention (pp. 972e1027). Oxford: Oxford University Press. Vallar, G., Burani, C., & Arduino, L. S. (2010). Neglect dyslexia: a review of the neuropsychological literature. Experimental Brain Research, 206(2), 219e235. Vallar, G., & Perani, D. (1986). The anatomy of unilateral neglect after right hemisphere stroke lesions. A clinical CT/Scan correlation study in man. Neuropsychologia, 24(5), 609e622. Vallar, G., & Ronchi, R. (2006). Anosognosia for motor and sensory deficits after unilateral brain damage: a review. Restorative Neurology and Neuroscience, 24(4e6), 247e257. Vallar, G., Rusconi, M. L., Fontana, S., & Musicco, M. (1994). Tre test di esplorazione visuo-spaziale: taratura su 212 soggetti normali. Archivio di Psicologia Neurologia e Psichiatria, 55(4), 827e841. Verdon, V., Schwartz, S., Lovblad, K. O., Hauert, C. A., & Vuilleumier, P. (2010). Neuroanatomy of hemispatial neglect and its functional components: a study using voxel-based lesion-symptom mapping. Brain, 133(3), 880e894. Von Hagen, K. O., & Ives, E. R. (1937). Anosognosia (Babinski), imperception of hemiplegia. Bulletin of the Los Angeles Neurological Societies, 2, 95e103. Vossel, S., Weiss, P. H., Eschenbeck, P., Saliger, J., Karbe, H., & Fink, G. R. (2012). The neural basis of anosognosia for spatial neglect after stroke. Stroke, 43(7), 1954e1956. Vossel, S., Weiss, P. H., Eschenbeck, P., & Fink, G. R. (2013). Anosognosia, neglect, extinction and lesion site predict impairment of daily living after right-hemispheric stroke. Cortex, 49(7), 1782e1799. Wilson, B., Cockburn, J., & Halligan, P. W. (1987). Behavioural inattention test. Titchfield, Hants: Thames Valley Test Company.