We calculated the false alarm rates for mean and non-mean trials for each participant in each hemifield. The 2 × 2 ANOVA on the group as a whole showed a significant interaction between Hemifield and Target Size, [*F(*1*,* 3*)* = 13*.*252 *p* = 0*.*036 η*p*2 = 0*.*815] but no significant overall main effects. Motivated by this interaction, we then examined each patient's data with the same bootstrapping method as described above. 3 of the 4 patients showed greater false alarms to the mean compared to the nonmean on the left side with 1 having very few false alarms and reversing (UNP1, *k* = 0*.*71, *p <* 0*.*0001; UNP2, *k* = 0*.*77 *p <* 0*.*0001; UNP3, *k* = 0*.*84, *p <* 0*.*0001; UNP4, *k* = 0*.*61, *p <* 0*.*0001). Conversely all four patients showed greater false alarms for the non-mean compared to the mean on the right side (UNP1, *k* = 0*.*47, *p <* 0*.*0001; UNP2, *k* = 0*.*45, *p <* 0*.*0001; UNP3, *k* = 0*.*75, *p <* 0*.*0001; UNP4, *k* = 0*.*27, *p <* 0*.*0006). **Figure 4** shows the false alarm rate for each patient.

# **DISCUSSION**

#### **VISUAL SEARCH**

Consistent with the neglect literature and visual search, patients' performance (as measured by hit rates) was worse on the left than the right side. All patients exhibited this pattern with hit rates on the left close to chance levels, consistent with unilateral neglect (see **Figure 3**). Each patient saw the search display for a different amount of time, as our goal was to keep the accuracy rate across the whole display as close to 70% as possible. We did this using the staircase method to adjust the duration of the search display throughout the experiment. The main question regarding visual search was whether performance differed between the right and left sides, and this was the case. When the left target was present, hit rates on the left hovered around chance performance (i.e., we were able to induce severe left neglect at these short stimulus presentations), while on the right it was well above chance performance. The difference in search between the two sides is consistent with fast and more efficient attentional deployment on the right compared to the left side of the display. This pattern is also consistent with left hemi-extinction, the less dramatic cousin to left unilateral neglect. When items occur on both sides of a display, left items are more likely to be missed. Since every trial had a group of irrelevant triangles opposite the circles, both sides were always filled with stimulation. As intended, these triangles appear to have attracted attention when they were on the right side (Eglin et al., 1989).

### **STATISTICAL SUMMARY**

However, the processes governing extraction of statistical summary appears to differ from those governing individuation of an object in search. Although this distinction has been proposed before in the literature with typical observers (Ariely, 2001; Chong and Treisman, 2003; Haberman and Whitney, 2007), there is no strong evidence for it in neglect patients. The present results demonstrate dissociation between performance measures for visual search and those for statistical summary. These can be seen most robustly in the false alarm rates on the left and right sides. When the target was absent most of the patients were more likely to say it was present when the average of the circle was the mean than when it was the non-mean. The opposite was true when the circles were on the right for all four patients (more false alarms to the non-mean than mean). If we consider the display

as a whole, the reasons for this pattern become clearer. Recall that during every trial, distractor triangles must be discounted in order for participants to form a statistical summary, consistent with the target size. If the triangles are not rejected, they will contribute to the estimate of the mean size—and skew the statistical summary. Returning to the scenario presented in the introduction, the neglect patients may be "pooling the clothes in the adjacent store window with the candy."

#### **DISTRACTORS**

This hypothesis is consistent with previous work on unilateral neglect suggesting that information presented on the neglected side is inappropriately filtered. For instance Kim (1997) used a negative priming paradigm in which two letters overlapped. One letter was the target (e.g., the red one), while the other letter was the non-target or distractor. Negative priming is indicated by a slower response to a distractor letter when it appears as a target on a subsequent trial. Results in patients with unilateral neglect demonstrated that negative priming is normal when displays are on the right side, but positive priming appears when displays are on the left side, indicating that the distractor letter was not inhibited. If this is the case, distractors in a statistical summary test may significantly impact extraction of the mean. Specifically, if information on the neglected left side is improperly filtered, the presence of distractors should compromise statistical summary on the right side of the display—and this is what we found.

**Figures 3** and **4** together suggest that statistical encoding took place implicitly even though controlled (explicit) attentional search of the left side was reduced. On the right side, the pattern of results did not support statistical processing. Indeed, the pattern of FAs was reversed (more FAs when the target was non-mean). We performed non-parametric tests on the right side to further statistically examine these results. Again, all patients showed a significantly greater effect to the non-mean on the right side. This skewed pattern of FAs indicates that statistical processing in the

right hemifield was disrupted. One interpretation of this result is that distractors could be rejected from the summary statistic when presented on the right side but not when presented on the left side.

# **IMPACT OF DISTRACTORS**

In order to further explore whether distractors presented on the left side are "encroaching" into the target pool (and thereby resulting in an erroneous statistical summary), we compared how distractor size affected performance when search display circles were smaller or larger. Importantly, distractor triangles are always the same size (the base of the triangle was similar in size to the largest circle diameter). However, circles within the search display varied in size, rendering distractors either more or less close to the circles mean size. This allowed us to observe whether the pattern of false alarms was affected by the distractors. The false alarm pattern presented in **Figure 5** provides provisional support that

subjects included distractors into their judgment of the mean when distractors were presented on the left side. Data from all participants are concatenated to increase the number of trials evaluated (as each participant saw only eight trials with small circles and eight trials with large circles). When distractors and display were different in size (**Figure 5B**), the pattern of false alarms is distorted (more false alarms to the non-mean compared to the mean). However, when distractors and display were similar in size (**Figure 5A**) the distorted pattern decreased. This is a small but not unexpected difference (given the small difference in mean size), and this would be the expected pattern if the triangles on the left were pooled with the circles displayed on the right.

# **SUMMARY**

Previous research indicates that unilateral neglect causes widespread disruption in attention, visual working memory, and spatial representation (Husain and Rorden, 2003; Malhotra et al.,

2005). These impairments negatively impact daily functioning in everyday life, resulting in problems with navigation, driving, reading, etc. While much is known about the disruptions in controlled attention and visual search, the role of statistical summary has only begun to be tested (Pavlovskaya et al., 2010, 2011). Here we tested patients who had recovered from clinical signs of neglect but continued to show neglect of the left side in a visual search paradigm and when display times were limited. There is some evidence from studies of patients with the neuropsychological diagnosis of Balint's syndrome that statistical summaries may be calculated from unattended information in the visual field (Riddoch and Humphreys, 1987; Demeyere and Humphreys, 2007; Demeyere et al., 2008). However, to our knowledge this is the first study to explore how the extraction of statistical summary may be affected by distractors in bilateral, grouped displays. This is a particularly relevant question because statistical summary in the real-world rarely, if ever, occurs without distractors.

and targets the same size. In panel **(A)**, differences between false alarms to

Our results show that patients with chronic neglect (as measured psychophysically) successfully segregated distractors on the right when targets were on the left side. They showed the expected pattern of statistical summary on the left—despite the fact that these patients allocated limited attention to this side (i.e., were at chance explicitly detecting the target). This result supports and expands Pavlovskaya et al.'s findings (2010, 2011), which suggested that neglected items contribute to explicit statistical summary estimates. Moreover, both findings reinforce Alvarez and Oliva's previous work with healthy normal participants, showing that statistical summary occurs even with reduced attention (Alvarez and Oliva, 2009; Joo et al., 2009; Haberman and Whitney, 2011) but extend this work by showing that statistical summary can be successfully performed by patients with unilateral attentional deficits. However, on the right side, patients showed more false alarms to targets that were the mean size compared to targets that were the non-mean size. One interpretation of this result is that neglect patients pooled distractors on the left side with targets on the right side causing the resulting statistical summary to be based on the display as a whole and thus distorted.

# **FUTURE DIRECTIONS**

impacting statistical coding.

These results imply that within real-world settings, neglect patients' ability to statistically summarize different sets of objects may be compromised. Future studies should further investigate whether altering the distractor features reduces the negative impact upon the statistical code in the right hemifield. For instance, our distractors, while different in shape, shared similar outline/filler color with the targets. It is possible that increasing the contrast in target outline/filler compared to distractor outline/filler will reduce pooling of targets and distractors. Further exploration of how distractor/target congruency interacts with statistical summary may yield a greater understanding of the neglect phenomenon and potentially contribute to rehabilitative programs.

Interestingly, the different pattern of performance between hits and false alarms suggests that statistical summary processes are distinct from object individuation. When the target was present, the patients exhibited the expected pattern of performance during visual search (poor performance on the left/better performance on the right). Whereas, when the target was absent, statistical coding dominates. This pattern reinforces previous research showing that object individuation operates independently from statistical summary mechanisms. For instance, neurologically intact participants can perform at chance when asked to individuate objects, yet, are still remarkably accurate in statistically summarizing across objects (Ariely, 2001; Haberman and Whitney, 2007; De Fockert and Wolfenstein, 2009; Haberman et al., 2009; Alvarez, 2011). Additionally Haberman and Whitney (2011), using change blindness paradigms, demonstrate that statistical summary occurs independent of change localization. We reinforce and extend these findings by showing that when object individuation does occur, it is distinct from statistical summary performance.

Our findings also raise interesting questions about how attention influences statistical summaries within normal populations. Chong and Treisman (2005) found that neurologically intact participants can successfully segregate items into different groups to produce separate statistical codes. However, they also found that the individual group averages were nonetheless affected by the overall average of both groups. Further studies should explore how distractors interact with the formulation of the statistical code, and specifically how reduced attention affects the filtering of distractors. Under impoverished attentional conditions (e.g., divided attention, peripheral viewing), can normal perceivers successfully segregate distractors?

# **CONCLUSION**

In conclusion, fundamental statistical summary abilities on the left side remained intact in patients who presented with unilateral neglect that had substantially abated but continued to be robust

# **REFERENCES**

on psychophysical tests. Under conditions that amplify neglect, the patients did summarize the statistics in a display. However, within the real-world, where targets and distractors are equally present within the visual environment, it is important to be able to pool information within different sets. We show for the first time that patients' with left sided attentional deficits, while not interrupting the averaging process *per se*, nonetheless alter summary statistics on the right side. Abnormal statistical coding may substantially affect patient functioning, as statistical summary operates on many levels of visual processing integral to daily life. Research has shown that it contributes to low-level processing (simple shapes), high level processing (faces and other complex stimuli), and visual working memory (Alvarez, 2011). Our work here, with chronic unilateral neglect patients, indicates that distractors encroach into summary coding of target displays, and the statistical summary fails to reflect veridical statistics of the target group. Such distortions may adversely affect the visual analyses of complex scenes in the real-world for such patients.

# **ACKNOWLEDGMENTS**

We would like to thank Amy Liu for assisting in data analysis. This research was supported by the Veterans' Administration and the National Institutes of Health Grant EY- 016975- 05 (Lynn Robertson) and the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0030097, Sang C. Chong). Lynn Robertson also has a VA appointment in VA Clinical Sciences Research Service, Department of Veterans Affairs Medical Center, Martinez, CA. She is a Senior Research Career Scientist.

mechanisms when counting and estimating. *J. Exp. Psychol. Hum. Percept. Perform.* 33, 1076–1088.

human vision. *Nat. Neurosci.* 4, 739–744.

distributions. *Ann. Math. Stat.* 19, 279–281.

**Conflict of Interest Statement:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

*Received: 21 February 2012; accepted: 10 September 2012; published online: 05 October 2012. 5*

*Citation: Yamanashi Leib A, Landau AN, Baek Y, Chong SC and Robertson L (2012) Extracting the mean size across the visual field in patients with mild, chronic unilateral neglect. Front. Hum. Neurosci. 6:267. doi: 10.3389/fnhum. 2012.00267*

*Copyright © 2012 Yamanashi Leib, Landau, Baek, Chong and Robertson. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.*

# **APPENDIX**

# Limb activation ameliorates body-related deficits in spatial neglect

#### *S. Reinhart 1 \*, L. Schmidt 1,4, C. Kuhn1, A. Rosenthal 1, T. Schenk3, I. Keller 2 and G. Kerkhoff 1,4*

*1 Clinical Neuropsychology Unit and Outpatient Service, Saarland University, Saarbruecken, Germany*

*2 Schön Clinic Bad Aibling, Clinical Neuropsychology, Bad Aibling, Germany*

*3 Department of Neurology, Erlangen University, Erlangen, Germany*

*4 International Research Training Group 1457 "Adaptive Minds", Saarbruecken, Germany*

#### *Edited by:*

*Mario Bonato, University of Padova, Italy*

#### *Reviewed by:*

*Alessandro Farne, Institut National de la Santé et de la Recherche Médicale, France Anna Berti, University of Turin, Italy*

#### *\*Correspondence:*

*S. Reinhart, Clinical Neuropsychology Unit, Building A 1.3., D-66123 Saarbruecken, Germany. e-mail<EMAIL_ADDRESS>Many neglect patients show deficits in the mental representation of their contralesional body side or body parts, termed personal neglect. These deficits include impairments in identifying body parts on schematic drawings of human bodies. Limb activation and alertness cues have been shown to modulate neglect transiently, and are effective treatments for several symptoms of the neglect syndrome. Here, we tested on eight patients with right-hemispheric stroke and left-sided spatial neglect whether these two techniques modulate deficits in the mental representation of hands, assessed with a hand-test in which the subjects had to decide whether a depicted schematic hand belongs to the left or right side of the human body. The results showed that neglect patients made marginally significant (*p* = 0.065) more errors in left-hand-decisions than right-hand-decisions, indicating a neglect-specific disorder. Moreover, we found that left-sided limb activation but not non-lateralized alertness cueing (a loud noise immediately before patients made their perceptual decision) significantly reduced misidentifications for depicted left hands as compared to baseline. No effect of any intervention was observed on error rates for depicted right hands. We conclude that the amelioration of the performance in the hand task is modulated by the activation of the body schema or other body representations through left-sided limb activation.

**Keywords: personal neglect, body schema, representational neglect, body representational neglect, limb activation, phasic alerting, treatment, rehabilitation**

# **INTRODUCTION**

Neglect as a failure to report, respond, or orient to contralesional stimuli (Heilman et al., 2000) may affect extrapersonal or personal space. Many of these patients fail to use or recognize the contralesional side of their body, an impairment which is termed personal neglect (Adair et al., 1995) or body representational neglect (Glocker et al., 2006). Personal neglect is frequently observed after lesions of the right hemisphere, but also after left hemispheric lesions (Groh-Bordin et al., 2009). The incidence is estimated to be up to about 45% in right hemispheric damaged patients, depending on the study and the used assessment instrument (Bisiach et al., 1986; Zoccolotti and Judica, 1991; Bowen et al., 2005; Groh-Bordin et al., 2009; Baas et al., 2011).

Personal neglect has been considered to be the origin of, or to be closely associated with, several neglect related impairments, including unilateral premotor deficits (Heilman et al., 1985), the misrepresentation of extrapersonal space (Bisiach, 1993; Umilta, 1995), and the disruption of the body-centered reference system (Karnath, 1994). However, although extrapersonal and personal impairments are often observed together as a symptom cluster in neglect patients, some studies using tests developed to assess personal neglect specifically like the Fluff-Test (Cocchini et al., 2001) the Vest Test (Glocker et al., 2006), or the Comb-and-Razor-Test (Beschin and Robertson, 1997; McIntosh et al., 2000) have found evidence of a double dissociation of these symptoms, both on the behavioral and anatomical level (Bisiach et al., 1986; Zoccolotti and Judica, 1991; Bowen et al., 2005; Committeri et al., 2007; Baas et al., 2011). Therefore, personal neglect seems to be only one aspect of the multifactorial heterogenous neglect syndrome that has been shown to occur in several sensory modalities and may also include motor neglect.

Disorders associated with body representational neglect include impairments of identifying body parts on schematic drawings of human bodies. As a possible origin of these impairments, some authors (Coslett, 1998; Baas et al., 2011) suggested an impaired mental body schema, respectively, a reduced access to this schema, which can be understood as a three-dimensional, dynamic representation of the spatial and biomechanical features of the own body (Coslett, 1998; Gallagher, 1998). Some authors postulate this mechanism to be responsible for the cortical representation of the trunk surface (Berlucchi and Aglioti, 1997) and peripersonal space (Graziano and Gross, 1998), whereas Cardinali et al. (2009) pointed out that peripersonal space and the body schema might be tightly related but distinct concepts with different sensory inputs (vision, audition, and touch vs. proprioception, kinesthetic, and touch), functional properties (defensive movements and voluntary actions vs. unconscious body knowledge for action), and neural mechanisms (parieto-frontal bimodal neurons vs. prefrontal and parietal cortex). Furthermore, other authors distinguish these space and action-related concepts from a semantic and lexical representation of the body (body part names, functions, and relations with objects), termed body image (Coslett et al., 2002; Schwoebel and Coslett, 2005). Even if the psychological validity of the concept "body schema" and the number of different body representations can be debated (Bisiach, 1993; Cardinali et al., 2009), there are several studies that support this concept (as defined above) with evidence (McCloskey, 1978; Lackner, 1988; Iriki et al., 1996; Maravita et al., 2003; Mussap and Salton, 2006). Moreover, the debates about the psychological validity of this concept may have in part been provoked by the inconsistent use of the term "body schema" in different studies (Poeck and Orgass, 1971; Gallagher, 1998; for a recent view on this topic see Berlucchi and Aglioti, 2010). For example, both body representational neglect and apraxia (Schwoebel et al., 2004) after left-hemispheric lesions are based on the concept of a body schema. Both disorders are associated with impaired knowledge about body parts, their position in space, and their spatial relationship. However, Groh-Bordin et al. (2009) found that the two disorders form a double dissociation at the behavioral and anatomical level.

Several studies indicated that healthy subjects use their own body schema to decide whether a depicted body part belongs to the left or the right side of the body (Cooper and Shepard, 1975; Sekiyama, 1982; Parsons, 1987a,b, 1994). For example, Parsons (1994) showed that the actual observer's own position affects the speed with which the observer can decide whether a depicted rotated hand (the palm or the back of a hand) is a left or a right hand. In his study, the subjects' reaction times for the left or right hand judgments were similar to the time the participants needed for a real movement of their own hand into the requested position. Therefore, it can be concluded that humans make those left-right judgments of displayed hands by mentally rotating the representation of their own hands (Cooper and Shepard, 1975; Sekiyama, 1982; Parsons, 1987b). Interestingly, Coslett (1998) found that patients with personal neglect are impaired in identifying depicted left-sided body parts. The patients were asked to name photographs of left or right hands. They labeled the right hand drawings more reliably than those of the left hand. In contrast, control patients without neglect did not name the left hands with a reduced reliability. Coslett (1998) concluded, that the impairment of patients with body neglect in identifying left hands is related to a disturbed schema of the left half of the body. In a recent study Baas et al. (2011) replicated this finding. Furthermore, judging errors for left hands were the best predictor of personal neglect compared to other variables like extrapersonal neglect, somatosensory or motor impairments, or deficits in the representation of the left-sided extrapersonal space. The results of Coslett (1998) and Baas et al. (2011) can be explained by the findings of Parsons et al. (Parsons and Fox, 1998; Parsons et al., 1998) according to which sensorimotor representations of the body or body parts are controlled by areas in the hemisphere contralateral to the limb. Therefore, it is plausible that lesions of these brain areas affect the mental simulation of movements that are associated with the correct identification of left or right hands. In summary, it can be hypothesized that the disruption of, or a reduced access to the actual representation of the own body features, the body schema, is responsible for the impairment of patients with body neglect in identifying left hands.

Based on different explanations of the neglect syndrome, several treatments have been developed and evaluated in the last decades (for review see Kerkhoff, 2003; Kerkhoff and Schenk, 2012). Most of them aim to modulate the rightward bias in spatial attention and exploration of neglect patients by providing additional sensory or motor input. One of these bottom-up treatments is limb activation. During limb activation, the patient is asked to make limb movements with their contralesional arm while performing spatial tasks. These movements reduce neglect symptoms, including motor impairments (Robertson et al., 2002), visual and sensory neglect (Robertson and North, 1993), and motor extinction (Robertson and North, 1994). Robertson and North (Robertson and North, 1992, 1993) favor the *active* movement of limbs to be the critical factor that alleviates neglect symptoms. Unfortunately, as many stroke patients suffer from paresis of the contralesional limbs or the whole contralesional side of the body, active limb activation is no appropriate treatment for a large group of patients. However, a few studies have shown that *passive* limb movements can improve neglect signs as well (Ladavas et al., 1997; Frassinetti et al., 2001; Harding and Riddoch, 2009). Several studies have shown that specifically the position of the left hand (which has to be placed in the left hemispace) rather than the active movement seems to be the critical factor to ameliorate neglect symptoms in the peri-personal space (Halligan et al., 1991; Robertson and North, 1993; Ladavas et al., 1997; Frassinetti et al., 2001). Therefore, the effects of passive as well as of active limb activation on neglect can be traced back to the additional (sensory) proprioceptive input which the limb movement provides.

Several attentional systems can be affected in neglect (Van Vleet et al., 2011). In addition to the pathological rightward bias in *spatial* attention, neglect patients often show an impaired *nonspatial* tonic alertness which is associated with large lesions of the right hemisphere including frontal areas (Wilkins et al., 1987; Pardo et al., 1991; Whitehead, 1991; Shallice et al., 2008). Several studies provided evidence supporting the idea that both attentional systems are closely linked and that impairments in tonic alertness may enhance the spatial bias of neglect patients to the right (Posner, 1993; Robertson et al., 1995, 1997, 1998; Sturm et al., 2006). Consequently, it is plausible that central alerting cues may alleviate spatial neglect. Robertson et al. (1998) examined this theory by having their patients make temporal order judgments whereby a left-sided, visually presented bar was preceded or followed by a similar bar presented on the right side. Neglect patients tend to perceive the right-sided stimuli first even when this stimulus was in fact preceded by the stimulus on their left side. Robertson and colleagues (1998) found that presenting a loud (centrally presented) noise just before patients take their decision will reduce this spatial bias.

In summary, there is ample evidence showing that limb activation and phasic alerting modulate a variety of visual or sensory deficits in patients with left-sided neglect. But what about deficits that are associated with body neglect? Studies evaluating effects of limb activation or alertness cueing on body neglect related symptoms, such as a disturbed body schema, are not available to the best of our knowledge, although body neglect is not an infrequent phenomenon after brain damage (Glocker et al., 2006). In the present study, we examined whether these two treatments have the potential to modulate the disturbed body schema of patients with personal neglect.

# **MATERIALS AND METHODS**

#### **PATIENTS**

Eight patients (Mean age = 61.1 years; SD = 12.1) with righthemispheric stroke and moderate to severe left-sided visual neglect (assessed with four conventional neglect screening tests, namely paragraph reading test, horizontal line-bisection, number cancellation and drawing figures; for details see Utz et al., 2011) were included. All patients also showed moderate to severe left-sided body neglect (see **Table 1**), assessed with the standardized vest test (see Glocker et al., 2006; Groh-Bordin et al., 2009). This test requires the blindfolded patient to search for 24 objects (12 on either trunk side) placed in pockets on the front side of a vest she/he wears, using his/her ipsilesional hand. The subject is required to search as quickly as possible for all objects and handle them to the experimenter. Normative values are available from 25 healthy subjects performing the test with their right hand, and 25 healthy subjects performing the test with their left hand (Glocker et al., 2006).

The mean interval from stroke to testing was 9.8 weeks (SD = 5.7). All subjects had a decimal visual acuity of at least 0.70 (20/30 Snellen equivalent) for the near viewing distance of 0.4 m (see **Table 1** for clinical and demographic details). Brain lesions were confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scans, and lesioned areas were mapped onto a standard MRI template using MRIcro software (Rorden and Brett, 2000). **Figure 2** shows lesion maps of six of the patients. From two patients (Pt. 4 and 8) radiological images were no longer available for lesion mapping. All participants were informed of the experimental protocol which was conducted in accordance with the Declaration of Helsinki II and gave their written informed consent prior to their participation in the study. The study was approved by the ethics committee of the Ludwigs-Maximilian-Universität, München/Germany, Project Nr. 352-09 in November 2009.

# **HAND TEST**

The hand-test used in the present study was developed based on the studies of Cooper and Shepard (1975); Parsons(1994); Coslett (1998). The stimuli included 24 schematic line drawings of the palm or the back of left or right human hands (see **Figure 1**). The stimuli (only one at a time) were presented centrally on a 15- computer screen in randomized order. The patients were asked to decide whether the drawing depicted a left or a right human hand and they were instructed to imagine their own hand to facilitate the identification of the drawings. The response time was not limited. To rule out visual comparisons of the own and the depicted hands, the hands of the patients were covered with a black blanket. The patients' verbal responses were recorded by one examiner. No feedback of their performance was given to the patient in any of the experimental conditions.

# **LIMB ACTIVATION AND ALERTNESS CUEING**

The patients sat in front of the computer screen with their eyes aligned with the center of the screen. For the passive-limbactivation intervention we adopted the protocol from the study of Frassinetti et al. (2001). During the assessment period the lower left arm of the patient was continuously stretched and flexed passively by an examiner up to a 45◦ angle and with a frequency of about 1.5 movements per second. The palm of the hand was

**Table 1 | Clinical and demographic data of the eight patients with left visual neglect after a single vascular lesion of the right hemisphere.**

*Abbreviations: MCI, middle cerebral artery infarction; ACI, anterior cerebral artery infarction; BG, basal ganglia; Th, Thalamus; FL, Frontal Lobe; TL, Temporal Lobe; PL, Parietal Lobe;* ∗*, No imaging available. Neglect screening tests:* −*, impaired;* +*, normal performance. Reading omissions: Paragraph reading of a 150 word reading test (normal cutoff max two omissions). Figure copy: Left sided omissions or distortions. Line bisection: normal cutoff max 5 mm deviation to the right. Number cancellation: normal cutoff: max two omissions on the left side (for details see Utz et al., 2011). Body neglect test: Vest test (see Glocker et al., 2006), cutoff scores: max three omissions for left/right side (from 12 targets on each trunk side);* ∗*Eight from eight patients were impaired for the left vest test side, seven from eight patients were impaired for the right vest side, but with a less marked impairment.*

oriented toward the patient. The elbow of the arm rested on the table in front of the patient on the left side of space, the upper arm, and the trunk forming an angel of about 35–55◦. As noted above, the moving left arm was covered with a black blanket and the right arm rested without any movement and invisible for the patient under the table on his right leg. The limb activation began 5 min before the hand-test task.

single stimulus (see Materials and Methods).

For the alertness-cueing intervention we adopted the protocol from the study by Robertson et al. (1998). The alertness cue (2200 Hz, 65–80 dB, 350 ms duration) was presented 1000 ms before the presentation of every visual stimulus via an external loudspeaker which was connected to the PC used for the visual stimulus presentation. To prevent spatial cueing the acoustic cue was presented from a central position relative to the observer's body midline in 0.80 m distance.

The patients were instructed to identify immediately after the presentation of the visual stimulus whether the picture represented a left or a right hand.

All experimental conditions were implemented in a randomized order to rule out sequence or test adaptation effects. The visual neglect tests were assessed at the beginning of the first and at the end of the second session. The whole experiment was realized within one week in two sessions of about one hour each.

### **RESULTS**

A *T*-test for repeated measurements (one-tailed) revealed a marginally significant difference between left- and righthand-judgments in the baseline measurement [*T(*7*)* = 1*.*710; *p* = 0*.*065]. An ANOVA for repeated measurements with the factors Treatment (Baseline, Limb Activation, Alertness Cueing) and Hand-Side (schematic pictures of left or right hands) revealed a significant effect of Treatment [*F(*2*,* 14*)* = 3*.*951; *p* = 0*.*044, η2 *p* = 0*.*361] and a marginally significant effect of Hand-Side [*F(*1*,* 7*)* = 5*.*029; *p* = 0*.*060; η2 *p* = 0*.*418]. The Treatment × Hand-Side interaction [*F(*2*,* 14*)* = 1*.*047; *p* = 0*.*377; η2 *p* = 0*.*130] was not significant. Subsequent *T*-Tests for repeated measurements were computed for a more specific examination of the treatment effects for each hand-side separately. For left hands the analysis (one tailed) revealed a significant reduction in decision errors for Limb Activation [*T(*7*)* = 2*.*200; *p* = 0*.*032; *d* = 0*.*77], but not for Alertness Cueing [*T(*7*)* = 0*.*659; *p* = 0*.*265; *d* = 0*.*23] compared to the Baseline. There was also a significant difference between the two treatments Limb Activation and Alertness Cueing [*T(*7*)* = −2*.*570; *p* = 0*.*037; *d* = 0*.*91; two-tailed]. For the right side, *T*-Tests revealed no significant differences between any of the conditions. Results are depicted in **Figure 3**.

*T*-Tests for repeated measurements revealed no significant differences between the first and the second assessment of the visual neglect paragraph reading test [left-sided word omissions; *T(*7*)* = 1*.*24; *p* = 0*.*25], horizontal line-bisection deviation [*T(*7*)* = −0*.*16; *p* = 0*.*89] and number cancellation [left-sided omissions; *T(*7*)* = −0*.*89; *p* = 0.40].

# **DISCUSSION**

In this study, we examined to which extent limb activation and alertness cueing can modulate signs of personal neglect assessed with a schematic hand discrimination task (left vs. right hand judgment). Unfortunately, there was only a marginal significant higher error rate for the identification of *left* hands as contrasted to depicted right hands. However, as the *p*-value (0.065) is close to the significance level of *p* = 0*.*05 our finding can cautiously be interpreted in line with the findings of Coslett (1998) and Baas et al. (2011) that neglect patients show a deficit in the identification of left hands related to their disorder. Several studies support the theory that subjects use their own body schema to identify depicted body parts, specifically hands. Therefore, the deficit of the participating patients in identifying left hands can be interpreted in favor of an impaired left-sided body schema (Coslett, 1998) for the left body side or in terms of a reduced access to this body representation of their left side. Another possible explanation is that patients with personal neglect principally could use their (unimpaired) body schema for hand identifications and simply do not use it because of their attentional neglect for the left side. Alternatively, it may be also hypothesized that this effect could be due to activation of other body representations beyond the body schema, i.e., body image, or motor imagery. This might explain why the body schema—which is typically conceived as an "unconscious" body representation—was modulated although our patients were explicitly (hence consciously) instructed to imagine their hands during the experiment.

Even if the effect of Hand-Side was only marginally significant and there was no significant interaction of Hand-Side × Treatment observable, we think that three significant effects are noteworthy because they possibly indicate an advantage of limb activation over alertness cueing in manipulating the disturbed identification of left hands in neglect. First, there was a significant main effect of Treatment indicating that the identification of depicted hands can be manipulated. Second, subsequent

analyses examining that effect revealed a significant reduction of misidentifications of left hands only during limb activation and no reduction during alertness cueing (both compared to the baseline). Third, there was a significant difference between limb activation and alertness cueing reflecting a greater reduction of misidentifications during limb activation. Therefore, it cautiously can be concluded that limb activation possibly has an advantage over alertness cueing in manipulating the disturbed identification of left hands in neglect patients. On the one hand, this result suggests that the body schema for left-sided body parts can be activated, at least in part, and therefore appears to be basically intact and accessible rather than completely destroyed. On the other hand, the results indicate that this activation has to be specifically *body-related*. An unspecific elevation of non-spatial alertness appears to be insufficient to alleviate the impairments in body representation observed in our small sample. However, as our results are not unambiguous and the lack of significance of the Treatment × Hand-Side interaction possibly is due to the small statistical power of our small sample, these hypotheses require further evaluation in subsequent studies with larger sample size.

These results would not only be of theoretical interest, but potentially also of clinical relevance. Passive limb activation has been found to decrease different neglect symptoms, particularly visual neglect (Ladavas et al., 1997; Frassinetti et al., 2001; Harding and Riddoch, 2009). Here we have shown that this treatment *transiently* modulates also the body schema which is disturbed in representational personal neglect. Currently we do not know whether it is also possible to obtain longer-lasting effects. Therefore, we will have to leave it to future research to determine whether limb-activation can be used as a treatment for personal neglect.

# **LIMITATIONS OF THE STUDY**

While the present results suggest—in our view—an interesting modulation of body-related deficits in patients with visual and body-neglect using limb-activation, there are several limitations. First, the sample size was limited. Second, no non-neglecting control group with right-hemisphere damage was included, thus, we do not know whether the observed manipulations are specific to neglect or would occur in other subjects (patients or healthy controls) as well. Moreover, the statistical analysis showed only a marginally significant effect of Hand-Side (close but beyond *p* = 0*.*05) and a non-significant Treatment × Hand-Side interaction. Finally, the precise mechanisms by which the typically unconscious body schema can be activated by an explicit (and hence initially conscious) instruction to imagine the own hands requires clarification in subsequent studies. Nevertheless, we believe that these admittedly preliminary results—which to our knowledge are the first on the modulation of this type of body-related deficits in spatial neglect—might stimulate interesting subsequent research. Furthermore, it might be interesting to evaluate whether such limb-activation effects might also be present in non-neglecting subjects, i.e., healthy subjects, or other clinical populations with body-related deficits, but without stroke.

# **REFERENCES**

extrapersonal neglect: a group study of their dissociation using a reliable clinical test. *Cortex* 33, 379–384.

same concept? *Brain Topogr.* 21, 252–260.

control of movement. *Curr. Opin. Neurobiol.* 8, 195–201.

and Weber, E. (1997). Auditory sustained attention is a marker of unilateral spatial neglect. *Neuropsychologia* 35, 1527–1532.

**Conflict of Interest Statement:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

*Received: 14 December 2011; accepted: 07 June 2012; published online: 22 June 2012.*

*Citation: Reinhart S, Schmidt L, Kuhn C, Rosenthal A, Schenk T, Keller I and Kerkhoff G (2012) Limb activation ameliorates body-related deficits in spatial neglect. Front. Hum. Neurosci. 6:188. doi: 10.3389/fnhum.2012.00188*

*Copyright © 2012 Reinhart, Schmidt, Kuhn, Rosenthal, Schenk, Keller and Kerkhoff. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits noncommercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.*

# Bisecting real and fake body parts: effects of prism adaptation after right brain damage

# *Nadia Bolognini 1,2\*, Debora Casanova1, Angelo Maravita1 and Giuseppe Vallar 1, 2\**

*1 Department of Psychology, University of Milano-Bicocca, Milan, Italy*

*2 Neuropsychological Laboratory, IRCCS Italian Institute for Auxology, Milan, Italy*

#### *Edited by:*

*Konstantinos Priftis, University of Padova, Italy*

#### *Reviewed by:*

*Lorenzo Pia, University of Turin, Italy Margarita Sarri, University College London, UK*

#### *\*Correspondence:*

*Nadia Bolognini and Giuseppe Vallar, Dipartimento di Psicologia, Università degli Studi di Milano-Bicocca, Piazza dell'Ateneo Nuovo, 1, 20126 Milano, Italy.*

*e-mail<EMAIL_ADDRESS><EMAIL_ADDRESS>
The representation of body parts holds a special status in the brain, due to their prototypical shape and the contribution of multisensory (visual and somatosensory-proprioceptive) information. In a previous study (Sposito et al., 2010), we showed that patients with left unilateral spatial neglect exhibit a rightward bias in setting the midpoint of their left forearm, which becomes larger when bisecting a cylindrical object comparable in size.This body part advantage, found also in control participants, suggests partly different processes for computing the extent of body parts and objects. In this study we tested 16 right-brain-damaged patients, and 10 unimpaired participants, on a manual bisection task of their own (real) left forearm, or a size-matched fake forearm.We then explored the effects of adaptation to rightward displacing prism exposure, which brings about leftward aftereffects. We found that all participants showed prism adaptation (PA) and aftereffects, with right-brain-damaged patients exhibiting a reduction of the rightward bias for both real and fake forearm, with no overall differences between them. Second, correlation analyses highlighted the role of visual and proprioceptive information for the metrics of body parts. Third, single-patient analyses showed dissociations between real and fake forearm bisections, and the effects of PA, as well as a more frequent impairment with fake body parts. In sum, the rightward bias shown by right-brain-damaged patients in bisecting body parts is reduced by prism exposure, as other components of the neglect syndrome; discrete spatial representations for real and fake body parts, for which visual and proprioceptive codes play different roles, are likely to exist. Multisensory information seems to render self bodily segments more resistant to the disruption brought about by right-hemisphere injury.

**Keywords: prismatic adaptation, space coding, body representation, multisensory, unilateral spatial neglect**

# **INTRODUCTION**

After an unilateral brain damage patients may show an altered representation of the space contralateral to the damaged hemisphere, that produces the neuropsychological syndrome of unilateral spatial neglect (USN). USN is more frequent and severe after damage to the right cerebral hemisphere, and involves the left portion of egocentric space in right-handed patients (Vallar, 1998; Bisiach and Vallar, 2000; Heilman et al., 2003; Husain, 2008; Vallar and Bolognini, in press). Basically, patients with USN show an inability to report sensory events occurring in the left side of space, contralateral to the side of the lesion (contralesional), and to perform actions in that portion of space. The deficit is dissociated from primary sensory and motor disorders, may be modality-specific, and conscious awareness may be more or less completely lost for the contralesional side of space. Patients with USN may show a variety of selective patterns of impairment, suggesting the existence of multiple spatial representations for different sectors of physical and imaginal space (Vallar and Bolognini, in press), and for specific stimuli, such as letter strings (Vallar et al., 2010). Particularly, USN may concern near extra-personal space or the body (Bisiach et al., 1986a; Guariglia and Antonucci, 1992; Committeri et al., 2007;Vallar and Maravita, 2009). These dissociations suggest

that the internal representation of the space around us, far from being unitary, includes a number of discrete, though related, components, with partly different neural correlates (Rizzolatti et al., 1997; Vallar, 1998).

One hallmark of the syndrome of left USN is a rightward deviation error in the task of bisecting a horizontal line (Schenkenberg et al., 1980; Bisiach et al., 1983; Vallar et al., 2000; but see Karnath and Rorden, 2012, for the view that a line bisection bias is not a core manifestation of USN). The line bisection task is a standard, simple test, widely used for the clinical diagnosis and the experimental investigation of USN. This task has been typically employed to explore the spatial representation, particularly the lateral extent, of extra-personal objects, most frequently segments (Schenkenberg et al., 1980; Bisiach et al., 1983; Halligan and Marshall, 1994; Vallar et al., 2000). Recently, we used this task to explore the spatial metrics of body parts in rightbrain-damaged patients with left USN, and in neurologically unimpaired participants (Sposito et al., 2010). Particularly, we demonstrated that USN patients show a rightward bisection bias for both their own left forearm and a three-dimensional extracorporeal object comparable in size (i.e., a plastic cylinder), as compared to control participants. However, analyses of group performance showed that the bisection error is minor for the forearm, in both USN patients (with a reduction of the rightward bias), and in neurologically unimpaired participants. Yet, single-patient analyses also reveal that in USN patients the rightward bias can be significantly more severe either in cylinder than in forearm bisection (the prevailing pattern, as indicated by the above mentioned group analysis), or, vice versa, in forearm bisection. This double dissociation suggests the existence of independent representations for extra-personal objects and body parts, likely supported by discrete spatial processes (Sposito et al., 2010).

In the same study we also performed a second experiment in neurologically unimpaired participants, investigating the mechanisms underlying the body part (forearm) advantage, using a fake forearm as the object, instead of the cylinder. No advantage for the real, as compared to the fake, forearm was found in the bisection task, suggesting that real and fake body parts share a common spatial representation, primarily based on a visuo-spatial code (Sposito et al., 2010).

The present study further explored the spatial representation of real and fake body parts in right-brain-damaged patients, with and without USN, and in neurologically unimpaired participants. The aim was twofold. First, we looked for putative differences in real vs. fake forearm bisection biases in right-brain-damaged patients, to explore the hypothesis (Sposito et al., 2010) that the involved representation is based upon a visuo-spatial coding of the metrics of body parts, with therefore no differences between real and fake forearm bisections. Second, we assessed the effects of prism adaptation (PA) on the bisection of (real and fake) body parts. Basically, PA consists in a short period of adaptive pointing toward targets optically displaced by prisms (Redding et al., 2005). As far as left USN is concerned, patients' exposure to prisms displacing the visual scene rightward, after adaptation through a visuo-spatial pointing task, brings about a leftward displacement in pointing ("aftereffects," occurring subsequent to prism removal), and an improvement of many manifestations of USN (Redding et al., 2005;Rode et al.,2006a). The mechanisms whereby PA operates are complex and debated (Rossetti et al., 1999; Redding et al., 2005). In USN patients adaptation to rightward displacing prisms may operate by restoring the egocentric reference frame, pathologically distorted rightward, and bringing previously neglected space into awareness. The manifestations of USN temporarily alleviated by PA include visual (Rossetti et al., 1998; Farnè et al., 2002; Vallar et al., 2006), haptic/somatosensory (McIntosh et al., 2002; Maravita et al., 2003a), auditory (Jacquin-Courtois et al., 2010), and representational (Rode and Perenin, 1994; Rossetti et al., 2004) deficits. We predicted that if real and fake body parts share a similar visuo-spatial representation, PA is expected to modulate their bisection bias in a similar way.

# **MATERIALS AND METHODS**

#### **PARTICIPANTS**

Participants were recruited from the inpatient population of the IRCCS Istituto Auxologico Italiano (Milano, Italy). All participants gave their informed consent to participate in the study. The protocol was carried out in accordance with the ethical standards of the Declaration of Helsinki (BMJ 1991; 302: 1194), and it was approved by the ethical committee of the IRCCS Istituto Auxologico Italiano.

Participants in the study included: 10 right-handed healthy subjects (i.e., Control Group, four males and six females; mean age: 56, range: 36–83; educational level: 9, range: 5–13), with no history or evidence of neurological disease; 16 right-handed righthemisphere-damaged patients (i.e., RHD Group, 5 males and 11 females; mean age: 60, range: 30–97; educational level: 12, range: 5–19). For the patients' groups, inclusion criteria were the presence of a right hemispheric lesion. All patients had no evidence of previous neurological disease or psychiatric disorders.

Contralesional motor, somatosensory, and visual field deficits, including extinction to tactile and visual stimuli, were assessed by a standard neurological examination; for each function tested (i.e., visual, somatosensory, and motor), the score range was: 3 = maximum deficit; 0 = unimpaired performance (Bisiach and Faglioni, 1974). Anosognosia for neurological deficits was assessed by the standard interview of Bisiach et al. (1986b), which provides scores ranging from 0 (no anosognosia) to 3 (maximum deficit).

Position sense disorders were assessed by using the test developed by Vallar et al. (1993). The patient's contralesional (left) forearm was placed on the bottom of a black box, which prevented patients from viewing the tested forearm. The upper limb was placed extended on a table, and the forearm was moved passively by the examiner to four different positions: straight ahead, 30˚, 60˚, and 90˚ adducted, with respect to the arm, toward the patient's trunk. In each trial, the starting point was a position with the forearm straight ahead; the forearm was repeatedly adducted and abducted before the intended position was reached. Patients received instructions to look in front of them while the examiner moved their arm to the intended position, and to communicate the perceived position of the arm, by pointing to the corresponding silhouette on the cover of the box. There were 40 trials (10 per position), in a random-fixed order. The score was the number of errors, i.e., a reported position of the forearm different from the actual position (error range: 0–40). The control participants' average error was 0.087 (range 0–2; Vallar et al., 1993).

The demographical and clinical details of each patient are reported in **Table 1**.

# **BASELINE NEUROPSYCHOLOGICAL ASSESSMENT FOR EXTRA-PERSONAL AND PERSONAL USN** *Cancelation tasks: letter, bell, star*

In the Letter task (Diller and Weinberg, 1977) the score was the number of "H"letter targets crossed out by each participant (53 on the left-hand side and 51 on the right-hand side of the sheet). Neurologically unimpaired participants made a mean of 0.13 (0.12%, SD ±0.45, range 0–4) omission errors out of 104 targets, with the maximum difference between omissions on the two sides of the sheet being two targets (Vallar et al., 1994). In the Bell task (Gauthier et al., 1989), the score was the number of "bell" targets crossed out by each participant (18 on the left-hand side, and 17 on the right-hand side of the sheet). Neurologically unimpaired participants made a mean of 0.47 (1.3%, SD ±0.83, range 0–4) omission errors out of 35 targets, with the maximum difference between omissions on the two sides of the sheet being four targets (Vallar et al., 1994). In the Star task (Wilson et al., 1987) the score

#### **Table 1 | Demographical and neurological data.**

*Etiology: I/H/A/T/TBI, ischemic/hemorrhagic/aneurysm/tumor/traumatic brain injury. Neurological examination: M/SS/V, motor/somatosensory/visual half-field deficits contralateral to the damaged hemisphere. Anosognosia: M/SS/V, for motor/somatosensory/visual half-field deficits. e, extinction to double simultaneous stimulation (for visual and somatosensory deficits);* ++*/*+*, severe/moderate deficit;* −*, no deficit; NA, not available. Position sense: n˚ errors out of 40 trials. N*−*, patients without USN; N*+*, patients with USN.*

was the number of small "star" targets crossed out by each participant (30 on the left-hand side and 26 on the right-hand side). Ten neurologically unimpaired participants (mean age: 72.2, SD: 5.27, range: 67–82; mean years of schooling 9.2, SD: 6.21, range: 3–18) scored 0.5 average omissions (0.9%, SD: ±0.7, range: 0–2), with the maximum difference between omission errors on the two sides of the sheet being one target (Fortis et al., 2010).

#### *Line bisection*

The patients' task was to mark 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 in width), presented in a random-fixed order. Each line was printed in the center of an A4 sheet, aligned with the midsagittal plane of the participant'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 measured to the nearest millimeter. A deviation score (percentage deviation) was then computed by means of the following formula: measured left half minus objective left half)/objective left half × 100 (Rode et al., 2006b; Sposito et al., 2010). This transformation yields positive numbers for rightward deviations, and negative numbers for leftward deviations. Control data for this version of the line bisection test were available from 65 neurologically unimpaired participants (mean age: 72.2, range: 65–83; educational level: 9.5, range: 5–18). The mean percentage of bisection error of the control group was −1.21% (SD ±3.48, range: −16.2 to +6.2%; Fortis et al., 2010).

#### *Five-element complex drawing (Gainotti et al., 1972)*

The patients' task was to copy a complex five-element figure: from left to right, two trees, a house, and two pine trees. Each element was scored 2 (flawless copy), 1.5 (partial omission of the lefthand side of an element), 1 (complete omission of the left-hand side of an element), 0.5 (complete omission of the left-hand side of an element, together with partial omission of the right-hand side of the same element), or 0 (no drawing, or no recognizable element). The total score ranged from 0 to 10. According to normative data from 148 neurologically unimpaired participants (age: range 40–79; education: range 5–13 years of schooling) a score lower than 10 indicated a defective performance (Fortis et al., 2010).

#### *Sentence reading (Pizzamiglio et al., 1992)*

Patients were asked to read six sentences. The score was the number of correctly read sentences (range 0–6). Ten control participants (see above, star cancelation) made no neglect-like errors, and 0.3 (5%, SD ±0.64, range 0–2) other errors (Fortis et al., 2010).

#### *Personal neglect test (Fortis et al., 2010)*

In this test patients were asked to reach six left-sided body parts (ear, shoulder, elbow, wrist, waist, knee), using their right hand. Each response was scored 0 (no movement), 1 (search without reaching), 2 (reaching with hesitation and search), or 3 (immediate reaching), with a 0–18 score range. Ten control participants (see above, star cancelation) made no errors (Fortis et al., 2010).

The patients' performance in each test is reported in **Table 2**. A pathological score in at least three tests was considered as an index of USN (see Fortis et al., 2010, for such a criterion); using this criterion, 7 out of 16 RHD patients showed USN (i.e., from patient P10 to patient P16).

#### **Table 2 | Assessment for visuo-spatial neglect.**

*Line bisection: percent deviation error (*−*/*+*, leftward/rightward). Cancellation tests: number of targets omitted in the left- and right-hand sides of the sheet (L/R), out of total targets. Asterisks: defective score, indicating left USN. Drawing, reading, and personal neglect tests: patient's score/maximum possible score (see text for details). NA, not available.*

#### **LESION DATA**

**Figure 1** shows the mapping of the brain lesions for the 14 out of the 16 RHD patients, for whom the original brain scan was available. Lesions were mapped using the software MRIcro (Rorden and Brett, 2000). We reconstructed the region of interest (ROI) to define the location and the size of the lesion for each patient by using a Template Technique, that is, by manually drawing the lesion on the standard template from the Montreal Neurological Institute. ROIs were created by mapping the regions on each and every 2D slice of a 3D volume.

#### **EXPERIMENTAL PROCEDURE** *Body bisection task*

Participants sat on a chair and were presented with a stimulus in front of them which could be either their own left forearm (real forearm condition) or a left fake forearm (fake forearm condition), placed at a distance of about 20 cm from the participant, with the objective midpoint aligned with their midsagittal plane. The fake forearm was a realistic, custom-made reproduction of a human male or female arm made by a scenic studio, and its length was broadly matched to that of a real forearm, as measured between the proximal and distal extremities of the ulnar bone (real forearm, controls = 23.6 cm ± 1.9; Patients = 23 cm ± 1.9; fake forearm = 24/22 cm, for a male/female forearm, respectively). During the bisection tasks, patients wore a black mantle; in the real forearm condition, each participant slid off the forearm from two side holes made in the mantle, so that only the forearm remained visible, while the hand and the arm above the elbow remained covered by the mantle; in the same way, in the fake forearm condition, only the fake forearm was out of the mantle (see **Figure 2A**). In both

conditions, the right and the left extremities of the forearm were marked by black tags, and were clearly indicated to each participant prior to each block of trials.

Participants rested their right index finger touching their body midline at the level of the sternum. In each trial, they were required to point with their right index finger to the perceived midpoint of each stimulus, considering the black tags as its right and left endpoints. Each pointing was performed once, with no time constraints and no corrections allowed. After each trial, the distance between the left side of the stimulus and the participant's pointing was measured to the nearest millimeter. The participant was then required to put the index finger back to the starting position, before the following trial. The bisection task, comprising both real and fake forearm conditions, was given to participants in two sessions, namely before and after a 10-min application of 10˚ right-shifting prismatic lenses during pointing (see below, PA). Stimulus condition was blocked in an ABAB (BABA) design, with each block comprising 12 trials for each stimulus condition (i.e., two blocks were administered before PA, and two blocks after PA). In sum, there were a total of 48 trials, 24 for each stimulus condition (i.e., 24 Real forearm bisections, and 24 Fake forearm bisections), 24 (12 Real, and 12 Fake) before and 24 after PA. The order of the Real and Fake conditions was randomized across participants. A percent deviation score was calculated for both conditions with the formula used for the line bisection test.

#### *Prism adaptation*

The procedure of Frassinetti et al. (2002), and of Fortis et al. (2010) was used. Each participant was seated in front of a table. A wooden box (height 30 cm, depth 34 cm at the center, and 18 cm at the two

sides, width 72 cm) was placed in front of him or her. The box was open on the side facing the participant ("proximal"), and on the opposite side ("distal"), facing the experimenter. On the experimenter's side (distal), the box could be made either open ("visible pointing"), or closed by a removable plexiglas ("invisible pointing" condition). In the visible pointing condition, the

black mantle, and they could see only their real forearm, which lay outside of two side holes of the mantle, or the fake forearm; black dots limited the extent of the real/fake forearm considered for the bisection task. **(B)** On the left, the box used for prism adaptation by repeated pointing trials, closed by the removable plexiglas, seen from the examiner's side (Fortis et al., 2010). Marks for the recording of the patients' pointing errors are shown. On the right, the prismatic goggles inducing a 10˚ shift of the visual field to the right.

participant's index finger came out of the box's open distal side, becoming visible to the participant. A visual target (a pen) was presented manually by the experimenter at the distal edge of the top face of the box (see **Figure 2B**). The visual target was presented randomly in one of three possible positions: central,straight ahead in front of the participant (0˚), lateral to the left (–21˚) or to the right (+21˚) of the participant's body midline. The distal edge of the top face of the box was graduated (in degrees), so that the experimenter measured the patients' pointing accuracy, namely the distance between their finger and the target, measured in degrees. A positive score denoted a rightward displacement with respect to the position of the target, a negative score a leftward displacement.

Participants were asked to keep their right hand, ipsilateral to the side of the lesion (ipsilesional) for right-brain-damaged patients, on their chest, at the level of the sternum (hand starting position) and to point with their right index finger toward the pen, at a fast but comfortable speed. The movement of the participant's pointing arm was executed below the top face of the wooden box, so that they could not see the arm's trajectory. Once the experimenter had recorded the patient's pointing performance, the patient retrieved the arm and prepared for the successive trial. The pointing task was performed in three experimental conditions: Pre-exposure, Exposure, and Post-exposure.

*Pre-exposure condition.* In this condition, immediately before wearing the prismatic goggles, participants were required to point with their index finger toward 60 targets presented randomly in one of the above mentioned three possible positions (20 targets at the center, 20 at −21˚ and 20 at +21˚). Participants performed the first block of trials (30) with visible pointing, and the second block with invisible pointing.

*Exposure condition.* Participants wore prismatic goggles (Optique Peter, Lyon, France), fitted with wide-field, prismatic lenses, inducing a 10˚ shift of the visual field to the right. Participants were asked to point with their right index finger to 90 targets presented in a random-fixed order in each of the three possible positions (30 targets at the center, 30 at −21˚, and 30 at +21˚). The pointing movement was hidden below the top face of the box, apart from its final part, where the index finger emerged beyond the distal edge of the top face of the box (visible pointing).

*Post-exposure condition.* Immediately after prism removal, participants were required to point to 30 targets (10 targets at the center, 10 at −21˚, and 10 at +21˚) in a random-fixed order. As in the pre-exposure condition, pointing was invisible.

### **STATISTICAL ANALYSES**

To assess the presence and amount of the aftereffects following PA, we compared the participants' pointing error in the preexposure and post-exposure conditions by a repeated-measures analysis of variance (ANOVA) with Group as a between-subjects factor (Control, RHD), and two within-subjects factors: Session (pre-exposure, post-exposure), and Target position (left, center, and right). The dependent measure in this analysis was the mean displacement (expressed as degrees of visual angle) of the participants' invisible pointing responses.

We also analyzed the visible pointing responses in the preexposure condition via a repeated-measures ANOVA with Group as a between-subjects factor, and Target Location as a withinsubjects factor.

Second, we assessed the effect of PA on the participants' performance in the body bisection task; the mean percentage of deviation errors was analyzed by a repeated-measures ANOVA with Group (Control, RHD) as a between-subjects factor, and two withinsubjects factors: Stimulus (real forearm and fake forearm), and Session (pre-exposure and post-exposure).

Moreover, in order to control for a possible effect of the lesion size in determining the body bisection pattern and the PA effect in RHD patients, we carried out an analysis of covariance (ANCOVA) on the RHD patients' mean bisection error with Stimulus and Session as within-subjects factor, and Lesion size (mean volume of the lesion = 90 cc, range = 40–25 cc) as covariate (the covariate was mean centered prior to the analyses).

For every analysis, we calculated the partial Eta Squared (*p*η2), which measures the proportion of the total variance that is attributable to a main factor or to an interaction (Cohen, 1973), and whenever necessary pairwise comparisons were conducted with the Newman–Keuls test. The level of significance was always set at 0.05.

To assess for the presence of any significant defective performance in individual RBD patients, we compared the deviation errors in the real and fake forearm conditions (considering the data before PA, i.e., the pre-exposure session) of each patient, with those of healthy participants. The comparison was performed by *t*-tests following the procedure of Crawford and Garthwaite (2005). Following the same procedure, we also compared the effects of PA on real and fake forearm bisections (i.e., the difference between the percent scores in the pre-exposure and post-exposure sessions) in each patient, with those of healthy control participants. Furthermore, following the Revised Standardized Difference Test (Crawford and Garthwaite, 2005), we compared in each patient the difference between real and fake forearm bisections in the pre-exposure condition, as well as between the effects of PA in the two bisection conditions, with the same differences in the neurologically healthy participants.

Finally, for right-brain-damaged patients, Pearson's correlation analyses were performed between the bisection error in the real and fake forearm conditions and the following variables: scores in the forearm proprioceptive test, in the standardized neurological exam (visual, tactile, and motor deficits), and in the clinical tests assessing USN.

# **RESULTS**

# **AFTEREFFECTS**

As **Figure 3A** shows, aftereffects (as indexed by the difference between the pointing errors during invisible pointing, before and after PA) took place after prism removal in controls and RHD patients. The ANOVA showed a significant main effect of Session [*F*(1,24) = 37.52; *P* < 0.001*, p*η2 = 0.99], with a larger leftward deviation (i.e., aftereffects) in the post-exposure (−2.1˚), as compared to the pre-exposure session (−0.36˚). The main effect of Target location was significant [*F*(2,48) = 13.39; *P* < 0.0001*, p*η2 = 0.86]: invisible pointing deviations to left target stimuli (−0.82˚) differed from central (−1.22˚,*P* < 0.01) and right (−1.65˚, *P* < 0.01) target stimuli; pointing to central and right target stimuli were different too (*P* < 0.02). Other main effects and interactions were not significant: Group [*F*(1,24) = 0.39; *P* = 0.5*, p*η2 = 0.02], Group by Session [*F*(1,24) = 0.26; *P* = 0.6*, p*η2 = 0.01], Group by Target location [*F*(2,48) = 2.11; *P* = 0.1*,*

*p*η2 = 0.08], Session by Target location [*F*(2,48) = 2.29; *P* = 0.1*, p*η2 = 0.09], Group by Session by Target location [*F*(2,48) = 0.73; *P* = 0.5*, p*η2 = 0.03]. The lack of significant interactions involving the Group main factor indicates that the size of the aftereffects was comparable across the two groups, as well as the pointing deviations to different target locations.

The analysis of visible pointing responses in the preexposure condition showed a significant effect of Target location [*F*(2,48) = 5.02; *P* < 0.01, *p*η2 = 0.2]: visible pointing deviations to left target stimuli (1.58˚) differed from central (1.12˚, *P* < 0.01), and right (0.99˚, *P* < 0.01) target stimuli; pointings to central and right target stimuli did not differ (*P* = 0.4). Other main effects and interactions were not significant: Group [*F*(1,24) = 3.12; *P* = 0.07*, p*η2 = 0.2], and Group by Target location [*F*(2,48) = 0.07; *P* = 0.9*, p*η2 = 0.01]. These findings suggest that both controls and RHD patients were equally accurate in pointing to visual targets in a baseline (with no prisms) condition.

#### **EFFECTS OF PRISM ADAPTATION ON BODY BISECTION**

**Figure 3B** shows that, in the Pre-exposure session, each group made a deviation error toward the right side in both the real and the fake forearm conditions, with a slightly more accurate performance in the real than in the fake forearm condition in RHD patients. RHD patients produced a larger rightward bisection error than neurologically unimpaired control overall. In the Postexposure session, in both stimulus conditions the rightward bias diminished in all groups, with a greater effect emerging in RHD patients. The ANOVA revealed a significant main effect of exposure Session [*F*(1,24) = 21.38; *P* < 0.0001*, p*η2 = 0.47], showing that both in controls and RHD patients there was a reduction of the rightward error in the estimation of the subjective midpoint of the real and fake forearms in the Post-exposure session (−0.51%, *P* < 0.001), as compared to the Pre-exposure session (5.13%). The significant Group by Session interaction [*F*(2,24) = 5.67; *P* < 0.02*, p*η2 = 0.37] showed that PA diminished the rightward bias in RHD patients only, in either stimulus condition (preexposure = +7.19% vs. post-exposure = −0.45%, *P* < 0.001), with no PA effects in control participants (pre-exposure = +1.85% vs. post-exposure = −0.6%, *P* = 0.3). RHD patients differed from control participants only in the pre-exposure session (*P* < 0.05), but not in the post-exposure session (*P* = 0.9). The main effect of Group [*F*(1,24) = 1.76; *P* = 0.2*, p*η2 = 0.07], and of Stimulus [*F*(1,24) = 0.02; *P* = 0.9*, p*η2 = 0.01], and the Group by Stimulus [*F*(2,24) = 1.69; *P* = 0.2*, p*η2 = 0.07], Session by Stimulus [*F*(1,24) = 1.81; *P* = 0.2*, p*η2 = 0.07], and Group by Session by Stimulus [*F*(2,24) = 0.23; *P* = 0.6*, p*η2 = 0.01] interactions were not significant.

The ANCOVA showed that the main effect of the covariate Lesion size, [*F*(1,11) = 2.38; *P* = 0.2, *p*η2 = 0.18] failed to reach significance. Moreover, Lesion size did not significantly interact with the main effects of Session [*F*(1,11) = 0.04; *P* = 0.8*, p*η2 = 0.01],and of Stimulus [*F*(1,11) = 0.12;*P* = 0.7*, p*η2 = 0.01], as well as with the Session by Stimulus [*F*(1,11) = 1.08; *P* = 0.3*, p*η2 = 0.09] interaction. Importantly, the main effect of Session was still significant [*F*(1,11) = 14.89, *P* = 0.01, *p*η2 = 0.58]. Hence, lesion size did not influence the performance of RHD patients.

Pearson's correlation analysis between the bisection error in the real and in the fake forearm conditions, for both the preexposure and the post-exposure sessions were also performed. In healthy participants, there was no significant correlation between real and fake forearm bisections both in the pre-exposure session (*r* = 0.42, *P* = 0.2), and in the post-exposure session (*r* = 0.11, *P* = 0.7). Instead, in RHD patients, there was a positive correlation between the bisection error in the real and in the fake forearm conditions in the pre-exposure (*r* = 0.72, *P* < 0.01), but not in the post-exposure session (*r* = 0.42, *P* = 0.1). Moreover, the amount of the aftereffects (post-exposure minus pre-exposure pointing error) was not correlated with the amount of shift in the body bisection task (post-exposure minus pre-exposure deviation error) both in controls (real forearm, *r* = −0.14, *P* = 0.7; fake forearm, *r* = −0.63, *P* = 0.06), and in RHD patients (real forearm, *r* = −0.12, *P* = 0.7; fake forearm, *r* = 0.17, *P* = 0.5). It may be noted that in controls a negative correlation between the size of the aftereffects and the bisection error for the fake stimulus approached significance.

#### **COMPARISON BETWEEN PATIENTS AND CONTROLS**

As shown by **Figure 4A**, before PA, 10 out of 16 RHD patients showed some degree of difference in the amount of error in one or both bisection conditions, as compared to controls. In particular, five patients had a significantly defective performance only in the fake forearm condition, showing a rightward error: P2 = +12% of deviation error, *t*(9) = 3.18, *P* < 0.01; P5 = +11% of deviation error, *t*(9) = 2.86, *P* < 0.01; P6 = +11% of deviation error, *t*(9) = 2.86, *P* < 0.01; P15 = +11%, *t*(9) = 2.86, *P* < 0.01; P16 = +13%, *t*(9) = 3.49, *P* < 0.01.  P5 and P8 also showed a significant difference between the two bisection conditions, with a greater rightward error for the fake forearm: P5 = +11%, *t*(9) = 2.77, *P* < 0.02; P8 = +18%, *t*(9) = 4.09, *P* < 0.01.

We also compared the performance of patients with or without USN in the two bisection conditions (real forearm vs. fake forearm) via an ANOVA with Group, as a between-subjects factor, and Stimulus, as a within-subjects factor; the dependent measure was the mean deviation error before PA. Only the factor Group was significant [*F*(1,14) = 8.15; *P* < 0.01*, p*η2 = 0.92]: patients with USN showed a larger rightward bisection error (+12%) in both the real and the fake forearm conditions, as compared to patients without USN (+3%). Other effects were not significant: Stimulus [*F*(1,14) = 2.38; P = 0.1*, p*η2 = 0.15], Group by Stimulus interaction [*F*(1,14) = 0.94; *P* = 0.4*, p*η2 = 0.03].

With respect to the effects of PA on bisection performance (i.e., the difference in the deviation errors between the post-exposure and the pre-exposure sessions, see **Figure 4B**), six RHD patients differed from controls in the fake forearm, showing a greater leftward error: P2 = −13%, *t*(9) = −3.18, *P* < 0.01, P8 = −21%,

*t*(9) = −5.72, *P* < 0.01, P11 = −24%, *t*(9) = −6.67, *P* < 0.01; P14 = −16%,*t*(9) = −4.13,*P* < 0.01; P15 = −18%,*t*(9) = −4.77, *P* < 0.01; P16 = −9%, *t*(9) = −1.9, *P* < 0.04. P1 did not show the typical leftward aftereffects, exhibiting instead a significant rightward deviation in fake forearm bisection after prism removal [+10%, *t*(9) = 4.13, *P* < 0.01]. Two patients showed significantly larger effects of PA in both the real and fake forearm bisections, which did not differ (*P* > 0.1): P10 = real forearm, −18%, *t*(9) = −3.81, *P* < 0.01, fake forearm, −12%, *t*(9) = −2.86, *P* < 0.01; P12 = real forearm, −21%, *t*(9) = −4.53, *P* < 0.01, fake forearm, −16%, *t*(9) = −4.13, *P* < 0.01. A significant difference between the aftereffects in the two forearm conditions was found in four patients, with a greater leftward shift for the fake forearm: P8 = 14%, *t*(9) = 2.85, *P* < 0.02; P11 = −16%, *t*(9) = 3.14, *P* < 0.01; P14 = −12%, *t*(9) = 2.45, *P* < 0.04; P15 = −14%, *t*(9) = 2.84, *P* < 0.02.

An ANOVA with Group (patients with vs. without USN) and Stimulus (real forearm vs. fake forearm) as main factors, run on the difference in the deviation error between post-exposure and preexposure to PA (post-PA minus pre-PA),showed a significant effect only of the factor Group [*F*(1,14) = 9.22; *P* < 0.01*, p*η2 = 0.85]: patients with USN showed a larger PA-induced leftward bias (−12%), as compared to patients without USN (−4%). Other effects were not significant: Stimulus [*F*(1,14) = 1.86; *P* = 0.2*, p*η2 = 0.12], Group by Stimulus interaction [*F*(1,14) = 0.48; *P* = 0.5*, p*η2 = 0.02].

# **CORRELATIONS BETWEEN FOREARM BISECTION AND CLINICAL SCORES IN RHD PATIENTS**

As reported in **Tables 3** and **4**, in RHD patients, only two significant correlations were found: the amount of visual deficit was positively correlated with the amount of the deviation error in both the real (*r* = 0.76, *P* < 0.01) and the fake (*r* = 0.77, *P* < 0.01) forearm conditions. Instead, the amount of proprioceptive deficit (i.e., position sense) was positively correlated with bisection performance in the fake forearm (*r* = 0.64, *P* < 0.01), but not in the real forearm (*r* = 0.41,*P* = 0.2) condition. No other significant correlations between performances in the experimental task and clinical scores were found.

# **DISCUSSION**

Two main results emerge from this study. First, in RHD patients, with and without USN, and in neurologically healthy participants, bisection performance is overall similar for one's own forearm

and for the fake forearm, as shown by the group analyses. As expected in a bisection task (see, e.g., Mancini et al., 2011, for a line bisection study comparing the performances of RHD patients with and without USN), RHD patients with USN make greater rightward errors in either stimulus conditions (i.e., real and fake forearm), than those committed by RHD patients without USN. These results are qualified by the single-patient analyses, which show that, as compared to healthy controls, 6 out of the 16 RHD patients (namely, P2, P5, P6, P8; P15, and P16, see **Figure 4A**) exhibit a pathological rightward bisection error only for the fake forearm, being statistically unimpaired for the real forearm (except for patient P8 who shows a defective performance also with the real forearm, but with a leftward bisection bias). Two patients (P5 and P8) show a significant difference between the real and the fake forearm bisections, with a greater rightward error in the fake forearm condition. As found in our previous study (Sposito et al., 2010), the forearm bisection deficit was unrelated to personal neglect (see **Table 1**).

The second finding is that all participants show PA and aftereffects. Overall, PA diminishes the rightward bisection bias in RHD patients in both real and fake forearm conditions, with no significant effects in control participants. The PA-induced leftward

**Table 3 | Correlation matrix between the bisection performances of RHD patients in the real and the fake forearm conditions, pre- and post-PA, and the demographic, neurological, anosognosia, and position sense (left forearm) scores.**

*Asterisk: significant correlation.*

*No significant correlations were found.*

bias in the real and fake conditions is greater in patients with USN, than in patients without USN. Moreover, analyses of the individual patients' performance, compared to healthy controls, show that, in 6 out of 16 RHD patients (P2, P8, P11, P14–16), PA reduces the rightward bisection bias in the fake forearm condition only. Furthermore, four patients (P8, P11, P14, and P15) show a significant difference between the effects of PA in the two stimulus conditions, namely: a greater increase of the PA-induced leftward bias for fake forearm bisection. Finally, in two RHD patients with USN (P10 and P12) PA brought about the leftward bias in both forearm conditions.

#### **REAL AND FAKE FOREARM BISECTION**

The overall lack of differences between the biases for the real and the fake forearm bisection tasks in right-brain-damaged and healthy participants shown by the group analysis, and the similarities of the effects of PA on the two types of stimuli, suggest that, at least as the present bisection paradigm is concerned, a shared spatial representation of real and fake body parts is available. The vision of a body part, as a highly specific and familiar object, may activate its prototypical standard representation, including spatial information about its length, thus allowing a comparable bisection performance for one's own forearm, and for a fake forearm, likely based on a visual analysis of the stimulus. The crucial role of visual inputs is supported by the significant correlation between the bisection performances in the two conditions, and the presence of a visual half-field deficit: the greater is the visual impairment, the larger is the bisection error in both real and fake forearm conditions. This finding is also consistent with the evidence that RHD patients with left USN and hemianopia make a greater rightward error in line bisection than USN patients without hemianopia (D'Erme et al., 1987; Doricchi and Angelelli, 1999; Daini et al., 2002). Notably, however, in RHD patients line bisection performance does not correlate with real and fake forearm bisection, in line with the recent previous evidence that different spatial processes are involved in the representation of extent, as assessed by bisection, of bodily and extra-personal objects (Sposito et al., 2010). Also fake and real forearm bisection performances do not correlate in healthy control participants, suggesting at least partly independent underlying processes, although caution is in order, since this conclusion is based on a negative finding. Interestingly, a significant correlation between the bisection performances in fake and real forearm conditions was found in RHD patients before, but not after, PA: this finding is likely to reflect the rightward-USN related bias shown by RHD patients, which affects both forearm types. The rightward error may however be differentially modulated by PA, according to forearm type, with effects confined to and greater in the fake forearm, as shown by the individual patients' analyses.

Importantly, we also found in RHD patients that an impaired position sense was related to the amount of deviation in fake, but not in real, forearm bisection. There is an important bodily illusion that might be relevant to explain why proprioceptive deficits are related to the ability of coding the spatial extension of the fake forearm. Visual capture of limb position is the phenomenon of perceiving the felt position of a limb to occupy the illusorily seen position when other sensory cues, such as proprioceptive

inputs, are in conflict (Giummarra et al., 2008). Proprioceptive input regarding the positions of body parts can drift them from their actual position when they are hidden from view (as it occurs in our experimental task; Gross and Melzack, 1978; Giummarra et al., 2008). An important example of this effect is the rubber hand illusion (RHI). The RHI is evoked when the participant watches a rubber hand being stroked, while their own unseen hand is stroked in synchrony. This results in feeling ownership over the rubber hand, and induces a relocation of the perceived position of one's unseen own hand toward that of the rubber hand (Botvinick and Cohen, 1998). However, the rubber hand produces no such modulatory effect when placed in an anatomically implausible posture, that is totally inconsistent with the real hands' actual posture. Thus, while purely visual information (i.e., the sight of a fake forearm) can dominate slightly discrepant proprioception (as in the case of the fake forearm, placed, as in our experiment, in a plausible position), a proprioceptive deficit may reduce the impact of vision when the visual information about the position of body parts is inconsistent with proprioception, and with the representation of the body schema. This multisensory, body-related mechanism may explain the similar performances in real and fake forearm bisections: under normal conditions, as in neurologically unimpaired controls (see also Sposito et al., 2010), the sight of a fake forearm in a possible anatomical location for the real forearm determines a visual capture effect of limb position; as a consequence, the fake forearm is processed as the participant's own real forearm, for the purpose of bisection. A different scenario emerges when position sense is impaired by brain damage: the visual capture of the fake forearm is compromised, as the disrupted proprioceptive input regarding the position of the real forearm cannot be drifted to the location of the fake forearm. Now, since the fake forearm is no longer processed as the real forearm, belonging to the participant's own body, the fake forearm ceases to benefit from a multisensory (visual-proprioceptive) code, that, in its proprioceptive component, is putatively crucial for real body parts, but is not available to fake body parts [unless there is embodiment of the fake forearm, see Giummarra et al., 2008]. Under these conditions, the fake forearm is now encoded as a mere extra-personal object, and becomes more susceptible to the spatial disruption brought about by damage to the right hemisphere, in line with previous evidence (Sposito et al., 2010).

This finding supports the idea that, although the visual appearance of the fake forearm as a body part may ensure, *per se,* a better spatial analysis as compared to a neutral object (Sposito et al., 2010), the proprioceptive input always plays a role in the spatial analysis of bodily related visual information.

The dissociations found in RHD patients further indicate that the metrics of real and fake body parts are supported by discrete spatial processes, that may be selectively disrupted by a brain lesion. As shown in **Figure 4A**, even some patients without USN show a selective impairment for fake, but not for real, forearm bisection (P2, P5, P6, and P8, the last patient, however, exhibits a leftward bias, namely no right USN, with the real forearm). Also, two patients with USN (P15, P16) are impaired in the fake forearm condition only, and an opposite dissociation is not found, suggesting that the representation of the length of self-body parts

is more reliable and resistant to the spatial disruption induced by a damage to the right hemisphere (see also Sposito et al., 2010).

Our findings are also in line with a dyadic model of body representation proposed in the literature, since the seminal studies of Bonnier (1905, see also Vallar and Rode, 2009), and Head and Holmes (1911; see for reviews: Berlucchi and Aglioti, 1997; Vallar and Papagno, 2003; Maravita, 2006; De Vignemont, 2010). A distinction has been drawn between a Body Schema, mainly constructed on somatosensory-proprioceptive and tactile information, which serves the guidance of actions, and a Body Image, which relies mainly on visual and tactile information, and mainly serves perception. Neuropsychological evidence shows that the Body Schema is actually dissociable from the Body Image. For instance, patients with USN are generally still able to perform non-conscious and automatic movements with neglected body parts, hence showing an intact Body Schema. Rather, the personal or bodily manifestations of USN appear to result from distortions of the Body Image, particularly affecting the conscious awareness of parts of the body (Sirigu et al., 1991; Gallagher and Cole, 1995; Coslett, 1998; Coslett et al., 2002; Gallagher, 2005; Maravita, 2006; De Vignemont, 2010; Preston and Newport, 2011). In this context, one may speculate that the Body Schema plays a pivotal role in the multisensory analysis of the metric of real body parts, whereas the visuo-spatial coding of fake body parts is a process pertaining to the impaired Body Image. The significant correlation between the severity of the proprioceptive deficit and that of the bisection error for the fake forearm suggests that, under unimpaired conditions, an object such as a fake body part may be processed as a real body part, namely as a part of the Body Schema, through computations involving position sense.

With respect to the neural correlates of deficits of real and fake forearm bisection, the limited number of patients, the different etiologies of the lesions, and the fact that some lesion images were not available for mapping, prevent definite conclusions. It may be cautiously noted, however, that the damage of the four RHD patients (P10, P11, P12, and P14) showing an impairment in the two bisection conditions is anterior-subcortical, affecting frontal areas, the insular cortex and subcortical structures including the putamen (see **Figure 1**). The frontal premotor cortex (PMC) and the putamen are known to instantiate a multisensory representation of peripersonal space. This representation is body part-centered, and it integrates visual, somatosensory, and proprioceptive information regarding stimulus location relative to the body (Graziano and Gross, 1993, 1995; Graziano et al., 1994; Maravita et al., 2003b). Moreover, in healthy humans, the experimental manipulation of ownership of individual body parts or of the whole body is associated with activity in PMC, the intraparietal sulcus (IPS), and the putamen (Ehrsson et al., 2004; Petkova et al., 2011). Finally, the insula has been definitely implicated in neurological disorders including anosognosia for hemiplegia, the sense of body ownership, the sense of agency and out-of-the-body experiences (Karnath et al., 2005; Baier and Karnath, 2008; Craig, 2009; Vallar and Ronchi, 2009; Berlucchi and Aglioti, 2010). Therefore, a damage to this network might disrupt the multisensory coding of the spatial extension of self-body parts, and the visual capture effect for fake body parts.

On the other hand, neuroimaging data suggest the existence of a posterior network concerned with a predominately visual representation of body parts; this network might play a crucial role in the selective deficit for fake forearm bisection, with spared real forearm. Indeed, the lateral occipito-temporal cortex includes a category-specific cortical region, the extrastriate body area (i.e., EBA), which responds in a selective manner to the visual presentation of real or stylized images of human body parts belonging to the participant or to someone else (Downing et al., 2001, 2006; Chan et al., 2004). Patients with posterior lesions including either the left or the right EBA are impaired in the visual processing of bodily forms,but not of bodily actions,while patients with anterior brain lesions, including either the left or the right ventral PMC, show an opposite pattern of deficits (Moro et al., 2008). Moreover, in humans, the lateral occipital cortex and the posterior part of the IPS (i.e., adjoining the transverse occipital sulcus) represent the hand-centered space in a predominantly visual manner, regardless of whether the hand is real or illusory, and with no relevant contribution of proprioceptive information about hand position (Makin et al., 2007). Instead, the anterior part of the IPS uses proprioceptive multisensory information in representing peri-hand space (Bolognini and Maravita, 2007, 2011; Makin et al., 2007). It may be noted that the one patient (P16) with a mainly posterior (temporo-occipito-parietal, see **Figure 1**) lesion is significantly impaired in the fake condition only, as compared with control participants. Also anterior lesions, however, may bring about this pattern of deficit (P2).

# **PA AND AFTEREFFECTS**

All participants showed aftereffects after PA, as assessed by the invisible pointing task, and the size of the aftereffects (i.e., the difference between pre- and post-PA invisible pointing performance) was comparable in the RHD and control participants. A recent study (Sarri et al., 2008), using a visual open loop pointing task (broadly comparable to our invisible pointing task), found that the error of patients with USN was comparable to that of neurologically unimpaired participants; crucially, the size of the aftereffects was comparable in patients with USN and in controls. A different pattern emerges when a dependent variable which has been considered an index of the neglect syndrome is used, namely the subjective straight ahead (Jeannerod and Biguer, 1987; Karnath, 1994, 1997; but see Farnè et al., 1998). Neglect patients show a larger rightward shift of the subjective straight ahead, assessed with participants being blindfolded, and greater effects of PA on this variable, as compared to healthy participants (Rossetti et al., 1998; Sarri et al., 2008). These findings may be interpreted as an indication that the disproportionate rightward shift of the subjective straight ahead is a pathological manifestation of USN, though it is not systematically found (Chokron and Bartolomeo, 1997; Farnè et al., 1998; Chokron, 2003); accordingly, in USN patients the effects of PA may be larger than in unimpaired participants (Sarri et al., 2008). With respect to line bisection performance, several studies (e.g., Colent et al., 2000; Berberovic and Mattingley, 2003; Michel et al., 2003; Fortis et al., 2011) have found a small neglect-like rightward bias on line bisection and Landmark tasks in normal participants following exposure to leftward, but not rightward, optical displacement; in patients with USN

some studies show a reduction of the rightward bias (e.g., Rossetti et al., 1998; Pisella et al., 2002; Redding et al., 2005, for review), others do not (e.g., Luauté et al., 2006; Nys et al., 2008; Fortis et al., 2010). In the present study, PA diminishes the rightward bisection bias only in RHD patients in both stimulus conditions (real and fake forearm, with no effects in control participants, supporting the view that these deficits are manifestations of the neglect syndrome brought about by right brain damage (Sposito et al., 2010). This is further supported by the comparison between patients with and without USN, which shows a greater PA effect on both the fake forearm and real forearm bisections in USN patients. On the other hand, the amount of the aftereffects is not correlated with the amount of shift in the real and fake bisection tasks both in controls, and in RHD patients. Notably, the present study, unlike the abovementioned previous reports (Rossetti et al., 1998; Sarri et al., 2008) included also RHD patients without USN, in addition to the patients with USN and the healthy participants.

# **REFERENCES**

Overall, these novel results demonstrate that in RHD patients PA affects the metric representation of the body, as indexed by forearm bisection performance, supporting the view that their rightward bias in real and fake forearm bisection is a manifestation of the left USN syndrome caused by the right hemispheric damage. Finally, the analysis of the performances of individual patients (showing in a number of patients effects on fake body bisection, and not on real body bisection) supports the view that the representations and processing of these two types of objects are, at least in part, independent.

### **ACKNOWLEDGMENTS**

This work was supported in part by MIUR and FAR grants from the University of Milano-Bicocca to Nadia Bolognini, Angelo Maravita, and Giuseppe Vallar, and by a Ricerca Corrente Grant from the IRCCS Italian Institute for Auxology to Giuseppe Vallar. We are grateful to Dr. Roberta Ronchi, PhD, for her assistance in patients' selection and lesion mapping.

extrapersonal neglect in humans. *Brain* 130, 431–441.

Weinstein (New York: Raven Press), 62–82.

improve contralesional tactile perception in neglect. *Neurology* 60, 1829–1831.

therapeutic tool for spatial cognition disorders. *Restor. Neurol. Neurosci.* 24, 347–356.

**Conflict of Interest Statement:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

*Received: 27 January 2012; accepted: 16 May 2012; published online: 05 June 2012.*

*Citation: Bolognini N, Casanova D,Maravita A and Vallar G (2012) Bisecting real and fake body parts: effects of prism adaptation after right brain damage. Front. Hum. Neurosci. 6:154. doi: 10.3389/fnhum.2012.00154*

*Copyright © 2012 Bolognini, Casanova, Maravita and Vallar. This is an openaccess article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.*

# Talking to the senses: modulation of tactile extinction through hypnotic suggestion

#### *Angelo Maravita1 \*, Mario Cigada1 and Lucio Posteraro2*

*1 Department of Psychology, University of Milano-Bicocca, Milano, Italy 2 Riabilitazione Specialistica, Ospedale di Suzzara SpA (MN), Italy*

*Edited by:*

*Konstantinos Priftis, University of Padova, Italy*

#### *Reviewed by:*

*Peter Halligan, Cardiff University, UK David A. Oakley, University College London, UK*

#### *\*Correspondence:*

*Angelo Maravita, Department of Psychology, University of Milano-Bicocca, Piazza dell'Ateneo Nuovo, 1, 20126 Milano, Italy. e-mail<EMAIL_ADDRESS>
Following brain damage, typically of the right hemisphere, patients can show reduced awareness of sensory events occurring in the space contralateral to the brain damage. The present work shows that a hypnotic suggestion can temporarily reduce tactile extinction to double bilateral stimulation, i.e., a loss of contralesional stimuli when these are presented together with ipsilesional ones. Patient EB showed an improved detection of contralesional targets after a single 20-min hypnosis session, during which specific suggestions were delivered with the aim of increasing her insight into somatosensory perception on both sides of the body. Simple overt attention orienting toward the contralesional side, or a hypnotic induction procedure not accompanied by specifically aimed suggestions, were not effective in modulating extinction. The present result is the first systematic evidence that hypnosis can temporarily improve a neuropsychological condition, namely Extinction, and may open the way for the use of this technique as a fruitful rehabilitative tool for brain-damaged patients affected by neuropsychological deficits.

**Keywords: hypnosis, neuropsychology, brain-damage, tactile extinction, rehabilitation**

# **INTRODUCTION**

Brain damage can deeply alter conscious perception of sensory events. A striking example of this is extinction to double simultaneous stimulation, whereby patients can detect unilateral stimuli on both sides of space, but fail to detect stimuli delivered to the side contralateral to the damaged hemisphere [more often left-sided stimuli following a right hemispheric lesion (Vallar et al., 1994a)], when these are delivered together with simultaneous ipsilesional ones (Bender, 1945; Bender and Diamond, 1975; Vallar and Maravita, 2009). Extinction is believed to originate from an abnormal competition for attentional resources between stimuli on opposite sides, which would cause the loss of the contralesional, "weaker," stimulus on bilateral presentations (Driver et al., 1997). A striking aspect of extinction is that, by definition, the deficit cannot be fully explained by a primary sensory loss (although this often co-exists), as shown by the correct detection of unilateral contralesional stimuli and by the evidence for various degree of implicit processing of the unreported targets (Maravita, 1997; Berti et al., 1999). The core deficit of these patients, therefore, would be at a higher level of perceptual processing, where sensory stimuli escape conscious detection after a certain degree of sensory analysis.

Extinction usually accompanies, or follows the more complex syndrome of Unilateral Spatial Neglect (USN), although it is dissociable from it (Cocchini et al., 1999). USN a complex, multicomponential syndrome in which patients fail to report bodily or extrapersonal stimuli delivered to the side contralateral to the damaged hemisphere (typically left-sided stimuli following a right hemispheric lesion), even if delivered in isolation (Heilman et al., 2003; Husain, 2008; Vallar and Maravita, 2009).

A clinically relevant feature of USN and extinction is that patients are typically unaware of their neuropsychological deficit (as well as of other co-existing primary sensory and motor deficits) a condition named anosognosia (Vallar and Ronchi, 2006). USN (Di Monaco et al., 2011), anosognosia (Gialanella et al., 2005) and to some extent even extinction (Rose et al., 1994) are regarded as negative predictors of outcome in brain-damaged patients with sensorimotor deficits. In particular, anosognosia seems to have a pervasive negative influence on the functional recovery after stroke (Gialanella et al., 2005) since it significantly limits the active participation of patients to any rehabilitation training. For this reason there is a strong need for a better understanding of these deficits and to find novel approaches by which residual sensory processing can be made available to awareness, even in patients who do not fully acknowledge their deficits and, therefore, are not likely to adopt explicit strategies to improve. Following these principles, many approaches have been proposed to date, such as vestibular stimulation (Cappa et al., 1987), neck muscle vibration (Karnath et al., 1993), TMS (Fierro et al., 2006), prism adaptation (Rossetti et al., 1998; Maravita et al., 2003), and limb crossing (Smania and Aglioti, 1995). These techniques have proved effective in producing short- or long-lasting improvements of USN and extinction in a "bottom up" fashion, i.e., without requiring the patient to adopt any explicit strategy.

In the present work hypnotic suggestion was used as a novel approach to modulate sensory extinction, and in particular tactile extinction. This technique is nowadays regarded as an important tool for studying sensory and cognitive brain functions (Oakley and Halligan, 2009; Raz, 2011) given its efficacy in modulating several electrophysiological and neurofunctional indexes (Rainville et al., 1997; De Pascalis, 1999; Maquet et al., 1999; Cojan et al., 2009), perceptual-cognitive effects (Szechtman et al., 1998; Kosslyn et al., 2000; Raz et al., 2007; Cohen Kadosh et al., 2009; Cojan et al., 2009; Casiglia et al., 2010; Priftis et al., 2011), clinical conditions (Oakley et al., 2002) or even simulating neurological or psychiatric conditions (Halligan et al., 2000; Blakemore et al., 2003).

During hypnosis, participants experience a peculiar condition (also indicated as "state of trance"), which is induced by the hypnotist through specific verbalizations. The nature of the "trance" state is still a matter of discussion. Researchers have found different physiological markers which would characterize the patient in hypnosis, including specific patterns of functional brain activations and deactivations (Maquet et al., 1999), changes in electrical cortical activity (De Pascalis and Penna, 1990) or increased activity in the anterior areas of the "default mode" network in highly susceptible individuals (McGeown et al., 2009). In the clinical practice, the hypnotic state is believed to help the patients accepting suggestions oriented at modifying their behavior not only while in hypnosis but, critically, even once the trance state is over (Erickson, 1980). In the present work we applied (although non-rigidly, as shown in the Methods section) a mainly indirect approach for delivering hypnotic suggestions, in line with the theoretical view outlined by Milton Erikson and currently used by many clinical psychotherapists (Erickson, 1980). This approach typically avoids proposing directive suggestions or the adoption of explicit behavior to the patient, but makes use of metaphoric statements or verbal descriptions that help patients building up insight into their deficit and stimulate the discovery of their own strategies for recovery (Williams, 1983; Matthews, 2000; Maudoux et al., 2007; Ross et al., 2007). Using this approach in hypnosis seemed an ideal way to improve neuropsychological deficits that typically escape the patient's awareness, such as extinction. In the present study we specifically targeted tactile extinction, with the aim of testing whether this deficit could be positively modulated by a single session of hypnosis in a right brain-damaged patient. The rationale of the hypnotic suggestions was that of guiding the patient towards a reduction of competition between the ipsilesional and the contralesional stimuli, following the idea of limited attentional capacity in these patients (Driver et al., 1997). While the rationale of this hypnotic approach was decided beforemeeting the patient, the details of the suggestions and the specific verbalization useful to reach that aim were decided online, following the imaginative contents produced by the patient during hypnosis.

# **CASE DESCRIPTION**

EB is a lively and cooperative 58 year-old, right-handed woman. Two years previous to testing she suffered a large ischemic stroke involving the insular, frontal and temporal regions of the right hemisphere (see **Figure 1**). Sensory and motor functions were briefly assessed through the standardized neurological examination by Bisiach et al. (1986). With this test both functions are examined according to a three-point scale ranging from score 0 (absence of deficit) to score 3 (maximum deficit). At the time of testing EB presented with left spastic hemiparesis (score 2 for the lower and 3 for the upper limb) and left hemianopia (score 3 for both quadrants). She also presented with USN and tactile extinction, as described below.

**FIGURE 1 | Magnetic Resonance images of EB's brain lesion.** Following the radiological convention, the right hemisphere is on the left side of the image.

# **ASSESSMENT OF TACTILE SENSITIVITY AND USN**

Tactile sensation and extinction were tested in the baseline assessment and in the experimental evaluations by computercontrolled devices (Foreman & Co., UK) producing single silent and invisible touches of 100 ms duration. The stimulators were taped on the distal pad of the forefinger of each hand while EB rested the hands on her lap and fixated a central mark placed on the table in front of her. Each testing session comprised the following stimulus types: 12 unilateral left, 12 unilateral right and 24 bilateral, plus 12 catch trials (no stimulation), for a total of 60 trials, delivered in random order within a single session. After each trial the examiner verbally prompted the patient to report the presence and the side of any perceived stimulus, recorded EB's response and started the following trial.

USN was formally tested in the baseline assessment and the experimental sessions, through common standardized tests, namely letter cancellation (Diller and Weinberg, 1977), star cancellation (Wilson et al., 1987), figure and shape copying test (Wilson et al., 1987), and sentence reading test (Pizzamiglio et al., 1990)1 .

1In the letter cancellation test (Diller and Weinberg, 1977) the patient was asked to mark all the "H" letters presented among other distracter letters and aligned in six horizontal lines. The score was the number of targets crossed out (53 on the left, and 51 on the right side of the sheet in total). The maximum difference between omission errors on the two sides of the sheet is two targets in neurologically unimpaired observers (Vallar et al., 1994b). In the star cancellation task the patient had to cancel star targets and ignore distracters (Wilson et al., 1987); the score was the number of correct targets crossed out (30 on the left, and 26 on the right-hand side in total). Ten comparable neurologically unimpaired participants tested in a previous experiment (Fortis et al., 2010) scored 0.5 omissions on average (SD 0.7, range 0–2), with the maximum difference between omission errors on the two sides of the sheet being one target. In the figure and shape copying test (Wilson et al., 1987), the score was given following a 0–4 range, based on the completeness of each drawn figure. The cut-off score for this test is 3. In the line bisection test the patient was requested to mark the midpoint of three 204-mm lines drawn on a single sheet of paper. The score range is 3–9, calculated on the amount of deviation from the objective center for each line, with a cut-off score of 7 (Wilson et al., 1987). In the sentence reading test patient was requested to read six sentences in Italian, consecutively presented in separate sheets of paper (score: 1 for each sentence read without omissions; score range: 0–6). Normal observers make no errors in this test (Pizzamiglio et al., 1990).

# **METHODS**

# **EXPERIMENTAL DESIGN**

The patient was tested in accordance with the guidelines of the Declaration of Helsinki, in eight sessions distributed over three days during a three-week period. Although the main focus of the hypnotic intervention was extinction, in all sessions EB was tested for tactile extinction and USN, apart from the last session when she was tested for extinction only. The patient was informed of the experimental procedure and that we planned to use hypnosis in order to improve her condition, in particular her perceptual functions, without explaining in full details the experimental design, in order not to influence her performance in the testing sessions. A full debriefing was given to EB at the end of the last experimental session.

The first day (day 1) comprised a first baseline testing of USN and extinction, plus an identical delayed baseline, that was performed after a 20-min interval occupied by an unstructured interview. The delayed baseline was performed in order to check for test–retest reliability of extinction and USN in a sequence comparable to that of the critical experimental sessions with hypnosis (see below). Furthermore, a third session was performed after EB was instructed to voluntarily orient her attention toward the left hand. This manipulation was introduced in order to compare the effect of a simple explicit attention-orienting strategy with the critical hypnosis suggestion. On the second day of testing (14 days after day 1), EB was tested before and after a preliminary hypnotic training (named Hypnosis-1) where she could familiarize with the induction of hypnosis, but without receiving any specific suggestion targeting extinction. On the third testing day (seven days after day 2) two further evaluations were performed, separated by the critical hypnotic induction (Hypnosis-2) specifically aimed at improving extinction, plus a further follow-up testing (Post-hypnosis-2 delayed), performed after 45 min in order to test for any delayed effect.

The number of correct responses in the different conditions was compared using planned Chi-squared tests.

# **DESCRIPTION OF THE HYPNOTIC INDUCTIONS**

#### *First induction (Hypnosis-1)*

This first hypnosis session had the following aims: collecting the clinical history and establishing a good therapeutic rapport with the patient and explaining to EB the principles of hypnosis, with explicit reference to this technique, and the aims of the procedure. Furthermore, in this experimental session the hypnotic induction was performed without any specific suggestion directed at influencing EB's sensory processing, but only as a training for reaching a good state of hypnosis and as a control for any unspecific effect of the hypnotic state on extinction.

A simple progressive relaxation technique, i.e., backward counting, was used by the hypnotist (one of the authors, Mario Cigada). This was meant to facilitate the hypnotic induction, also given that EB appeared very distractible and manifested some difficulty in paying attention to the hypnotist's voice. After some relaxation was obtained, the hypnotist asked the patient to imagine herself in a pleasant place and describe what she imagined. EB referred that it was difficult for her to try and visualize anything, and her level of relaxation was waxing and waning for some

time, with frequent interruptions of the hypnotic induction procedure, in which the patient started talking to the hypnotist about her clinical condition. The relaxation procedure was repeated a few times, since EB appeared more focused on the words of the hypnotist. At this stage, EB was able to relax quite easily and spontaneously recollected a trip to Athens occurred 30 years before, describing many images and details. The patient appeared to reach a good level of trance, as suggested by some overt behavioral signs, such as spontaneous eye closing, reduced loudness and tone of the voice, reduced facial expressions, absence of unrequested voluntary movements, decreased breath frequency and muscular relaxation that included the upper and lower limb on the plegic side 2 . In particular we observed a visible reduction of spasticity on the left hand as a consequence of muscular relaxation. This was of much surprise for the patient's daughter, who was present during the hypnosis session, since a reduction of the left hand spasticity was usually very difficult to obtain. After about 15 min, the hypnosis was terminated and the patient showed a sudden change of trunk posture and successive postural adjustments on the wheelchair, eye opening and gaze re-orienting, all suggesting that she was out of the hypnotic state.

# *Second induction (Hypnosis-2)*

The aim of the second experimental session was to influence the contralesional tactile extinction by specific suggestions during the hypnotic state.

The hypnotist started by using the same progressive relaxation technique (backward counting) used in the previous hypnotic session, in order to reach a state of concentration and relaxation. Again the procedure was initially quite effortful for the patient and required a few minutes to be effective. The trance was progressively deepened by the recall of several pleasant sensations experienced spontaneously by the patient in the previous session. After EB seemed to have reached a trance state, as suggested by similar behavioral signs of as those described above (including, again, visible muscular relaxation with reduced spasticity), the patient spontaneously recalled a car trip to the seaside. EB described the landscape that she imagined to see through the car window. A suggestion was then given that "the windscreen is misted over and that she can try and make left-sided images brighter by cleaning it." After a while the imaginary trip took EB over a bridge on the Po River (located in the North of Italy). The patient became quite emotional at this memory and her level

2The deepness of the hypnotic trance was systematically assessed using a custom-made questionnaire. The questionnaire is divided in two sections: the first comprises direct questions that are asked to the subject immediately after hypnosis to quantify his/her experience, the second is a check list in which a number of behavioural signs, observed in the participant during the trance state, are scored. Although this tool is not meant to score the hypnotic susceptibility but to qualify the actual experience of hypnosis, the scores at this questionnaire have been found to show some degree of correlation with the Stanford Hypnotic Susceptibility Scale (*r* = 0*.*47; *p <* 0*.*01) (data presented at the XI National Meeting of the "AMISI"—Italian Medical Association for the Study of Hypnosis-1998 Firenze "Quarant'anni di ipnosi in Italia:presente e futuro" G. Mosconi ed.). EB reached a score of 43% (a percent score relative to the maximum possible score) for the Hypnosis-1 and 46% for the Hypnosis-2 sessions. Such scores indicate that the patient reached a good, albeit not deep, hypnotic state.

of concentration decreased. After EB was again relaxed, she was invited to "imagine to dip both hands into the river's fresh water and try and experience how pleasant is to play with the sensations coming from both hands, for example, by reducing the sensitivity of the right hand and increasing that of the left hand." The patient found this exercise pleasant and easy to perform. The sensory manipulation was suggested a few times and it was also suggested that she "could keeping on playing with the sensitivity from the hands as if she was performing a physical training, in order to get stronger and feeling better, and that she could learn this pleasant exercise and repeat it from time to time in her daily life." The rationale of this statement was to favor EB's insight into tactile experience from both hands, by suggesting a positive association between somatosensory imagery and physical health, with the final aim of an improvement of extinction. The suggestion that this exercise could be repeated in the future as a sort of healthy training was aimed at anchoring EB's experience in hypnosis with her daily life, in order to help her favoring a process of self-healing.

The patient suddenly started crying, while recollecting her mother, who died a few years before and who joined the patient during that trip to the river. After she felt calmer, EB's somatosensory imagery was again stimulated by inviting the patient to "visualize her body walking around, and to concentrate on the somatosensory sensations coming from the movement of the left and right sides of the body." After EB has concentrated on this task for a while, describing sensation of touch, pressure, and temperature coming from her body, she was asked to slowly end her imaginary, and hypnosis was terminated. Again EB showed clear signs of sudden, spontaneous postural and attentional re-orienting. This session of hypnosis lasted around 20 min.

# **RESULTS**

### **BASELINE TESTING OF EXTINCTION AND USN (TABLES 1, 2)**

When tested for tactile extinction EB showed perfect detection of right-handed stimuli, reduced sensitivity on the left-handed stimuli (8 out of 12 correctly perceived) and 100% extinction of the left touches on bilateral stimulations (**Table 1**). There were only occasional responses to catch trials, always consisting in the false perception of unilateral left touches. Furthermore, clear signs of USN were present in all tests (**Table 2**). EB was deeply unaware of her defective performance in extinction and neglect testing. Although she had a good awareness of her motor deficits, she generally attributed any other deficit of the daily life, i.e., neglecting objects on the left side, bumping into doorways or impaired reading abilities, to fatigue and impaired vision.

# **EFFECTS OF HYPNOSIS ON TACTILE EXTINCTION AND USN (TABLES 1, 2)**

When tested for extinction (**Table 1**), EB showed a fluctuation in the performance on left unilateral trials across all sessions. On the other hand, there was a very clear and reliable pattern for the double bilateral stimulations: In the first two baseline sessions the left stimulus was never detected. Similarly, in the third session, when EB was instructed to orient her attention toward the left side, there was a non-significant increase of correct perception of bilateral trials (1/24 correct), but also an increase in

*Percent of correct responses to unilateral and bilateral trials in the different testing sessions. Errors on bilateral trials always consisted of the omission of the left-sided stimulus. Errors on catch trials always consisted of the false report of a left-sided stimulation.*

false alarms (8/12) [CHI2(1) = 0,980, *p* = 0*.*3 and CHI2(1) = 2.5; *p* = 0*.*1, respectively]. This pattern suggests the adoption of an overall less conservative criterion in reporting left targets, following the attentional shift. Even the first hypnotic induction (Hypnosis-1) produced no effect on extinction. By contrast, after the second (specific) hypnotic session (Hypnosis-2) the perception of left touches on bilateral trials critically improved (8/24 stimuli correctly reported post-hypnosis vs. 0 pre-hypnosis, CHI2 (1) = 5,4; *p <* 0*.*05), with no difference in false alarms (100% correct) (**Table 1**). The improvement was still observed in the delayed post-hypnosis testing (6/24 stimuli correctly reported, CHI2 (1) = 4.5, *p <* 0*.*05). Also the response to left unilateral trials showed a marginally significant improvement in both the immediate and delayed post-hypnotic testing sessions (100% correct for both sessions vs. 9/12 correct before hypnosis, CHI2 (1) = 3.4, *p* = 0*.*06).

At odds with extinction, which showed remarkably stable results before the critical Hypnosis-2 session, the scores on most tests for USN showed a progressive improvement going from the first to the last repetition of the neuropsychological assessment (**Table 2**). More specifically, in the sentence reading test, some improvement was present in the baseline testing, in the unspecific hypnosis session, but not in the critical Hypnosis-2 session. In the figure and shape copying task, the amount of improvement in the critical Hypnosis-2 session was the same as in the baseline. The star cancellation was the only test showing some improvement in the Hypnosis-2 session, although some improvement was also found in the baseline test, while letter cancellation actually showed a worsening after hypnosis. Finally the line bisection showed no effect in the Hypnosis-2 session. Overall, the improvement found from the first baseline to the pre-Hypnosis-2 session was in most cases comparable, or superior, to that found following the critical Hypnosis-2 session and is likely due to unspecific learning effects, caused by the numerous repetitions of the testing battery. Due to this general pattern, and to the main target of the experimental procedure, which was extinction, USN scores were not further analyzed.

#### **Table 2 | Neuropsychological evaluation of USN.**

*Scores on the neuropsychological tests for USN in the different experimental conditions (see text for the scoring procedures and the asterisk indicates abnormal performance.*

# **DISCUSSION**