Virtual image grasping in patients with Alzheimer-type dementia

Neuroscience Letters 299 (2001) 101±104

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Virtual image grasping in patients with Alzheimer-type dementia Walter Massing a,*, Marlene Kenklies b, Klaus Hager b b

a Psychiatric Day Clinic, Clinicum Hannover, KoÈnigstrasse 6a, 30175 Hannover, Germany Department of Geriatrics and Rehabilitation of the Henrietten Foundation, 30559 Hannover, Germany

Received 17 November 2000; received in revised form 20 December 2000; accepted 20 December 2000

Abstract Patients with various neuropsychiatric disorders who confused virtual images with real objects have recently been described. When asked to take objects from an investigator's hand while looking in a mirror, these patients reached directly into the mirror for the object's image. To investigate whether the phenomenon occurs in patients with Alzheimer's disease, we studied 127 cases, of whom 67 were suspected of having Alzheimer-type dementia (DAT). The phenomenon in question was not observed in either of two control groups, but whereas 38 (57%) of the DAT patients responded correctly, 17 (25%) of them grasped at the mirror image. Characteristically, none of the eight patients who grasped into the mirror and underwent single photon emission computed tomography analysis showed symmetric activity. We also analyzed the behaviour and verbal utterances of the DAT patients in front of the mirror. q 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Virtual image grasping; Mirror image; Alzheimer-type dementia

Is a mirror image real? No, surely not [9,10]. But humans can usually reconstruct the world coordinates of a real object that is the source of a mirror image. It has recently become evident that, with certain disorders, the ability to take an object from an investigator's hand while looking in a mirror has been lost. Ramachandran et al. [13] reported four right-hemisphere stroke patients who had left visual ®eld `neglect'. They were indifferent to objects in their left visual ®eld even though they were not hemianopic. In their experiments, Ramachandran et al. [13] offered the patients an external aid to overcome their dif®culty in paying attention to the left side. They placed a mirror on the right side of the patient in order to provide an indirect way for them to perceive their left (neglected) side. However, these patients reached into the mirror or claimed that the object was behind the mirror. One interpretation of Ramachandran et al. [13] was that, since their patients were suffering from left hemispatial neglect, they were making inferences such as the following: `Since the re¯ection is in the mirror, the pen must be on my left. But the left does not exist in my world, therefore it must be inside the mirror'.

* Corresponding author. Fax: 149-511-3884871. E-mail address: [email protected] (W. Massing).

In a similar way, Binkofski et al. [2] described ®ve of 13 patients who were unable to distinguish between a real object and a mirror image. These patients located the object in or behind the mirror and guided their hand directly towards the image in the mirror. In contrast to Ramachandran et al. [13], Binkofski et al. [2] concluded that neither hemi-neglect nor right parietal lesion are necessary conditions for mirror agnosia. The implications of such failure to distinguish clearly between a perceived image and an object have recently been studied in some detail (Massing, unpublished data) in four patients with senile dementia of the Alzheimer's type (SDAT). Three of them, who were unable to recognize themselves in a video recording, attempted to grasp re¯ected objects from a laterally positioned mirror and televised objects from a video monitor. The correspondence between their own movements and their re¯ected movements enabled the three patients to recognize themselves in a mirror and to take the object out of the investigator's hand while looking into the frontal mirror. In order to ®nd support for the results of this preliminary case study and in order to determine the frequency of the phenomenon in Alzheimer's disease, we ®rst made a study of 67 cases suspected of having Alzheimer-type dementia (DAT). We also studied 30 age-adjusted normal patients as well as 30 age-adjusted patients with various neurological

0304-3940/01/$ - see front matter q 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S03 04 - 394 0( 0 1) 01 50 0- 2

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W. Massing et al. / Neuroscience Letters 299 (2001) 101±104

disorders such as post-hypoxic condition, multiple sclerosis, and so on. The phenomenon in question was not observed in either control group. As in the previous experimental set-up (Massing, unpublished data), we requested the patients to stand close to a 180 £ 120 cm free-standing mirror, ®rst with their right side (right lateral mirror) and then with their left side (left lateral mirror) towards the mirror. The investigator stood at the side of the patient furthest from the mirror but facing it. He then held an object in the mirror and within the patients' reach so that they could see it when they looked sideways into the mirror. The patients were ®rst asked to identify the object held by the investigator and then to grasp the object while looking at its re¯ection. The objects were of different size and type, such as a bottle of mineral water, a pen, a bunch of keys, a video-cassette and so on. Afterwards the patients had to stand directly in front of and facing the mirror (frontal mirror). With the patients facing the mirror this time, the investigator stood behind them ®rst to the right (right frontal mirror) and later to the left (left frontal mirror) and presented the above-mentioned objects so that they could be seen and reached. In each case the subjects had to take the object out of the investigator's hand. All patients were fully aware of the experimental situation and of the meaning and use of a mirror, and they were all able to identify themselves in the mirror. The average age of the 41 male and 26 female DAT patients was 68 (range 51±87 years), and the average duration of the illness was 2 years, 10 months (range 2 weeks±8 years). We carried out imaging procedures and extensive psychological tests with all the patients at the same time. In the mirror test, 38 out of 67 (57%) of the DAT patients responded correctly, whilst 17 (25%) grasped at the mirror image, six (9%) showed absolutely no reaction to the request, and the response of six (9%) was not clear. For details see Table 1. We compared the group of DAT patients who had responded to the test correctly with the group of those who had attempted to grasp at the mirror image and with

Table 1 Results of the evaluated video recordings a N

ls

rs

lf

rf

38 1 5 1 2 1 7 12

1 1 ù ù ù 1 ù ?

1 ù ù ù 1 ù ù ?

1 1 1 ù ù ù ù ?

1 1 1 1 ù ù ù ?

a

N, number of cases; ls, mirror on the left side; rs, mirror on the right side; lf, mirror frontal and object on the left side; rf, mirror frontal and object on the right side; 1, grasping the real object; ù, reaching for the virtual object; ?, inadequate reaction.

the group of those who did not show any reaction at all. The three groups were clearly distinguishable on the basis of the results of the Benton Test (ANOVA 6.26, 8.65, 9.67, F ˆ 10:640, P , 0:0001), of the ADAS (ANOVA 27.0, 46.18, 48.33, F ˆ 13:268, P , 0:0001) and the `clock drawing' test study (ANOVA 3.06, 4.62, 5.4, F ˆ 6:681, P , 0:001), and showed systematic deterioration from group 1 to group 2 to group 3. The patients' ages and the commencement and duration of the illness did not have any in¯uence on the test performances. In 47 cases (70%) we carried out a single photon emission computed tomography (SPECT). Twenty minutes were allowed to pass for the patients to relax. No sedative or tranquilizing substances had been given. The lights were dimmed and the rooms kept quiet during the 15-minute brain uptake phase after injection of Tc labelled HMPAO. One hour after injection, SPECT images of the brain were obtained. Characteristically, of the eight patients who grasped into the mirror and had SPECT conducted on them, none showed symmetric activity. Only two of them exhibited primarily left-sided hypoactive regions, while six exhibited primarily right-sided hypoactive regions. In order to make the SPECT results amenable to discriminant analysis, the more differentiated results of SPECT were simpli®ed using a parameter where one refers to symmetrical brain activity, two to left-sided hypoactive regions and three to right-sided hypoactive regions. With the above-mentioned three-group variable and the variables ADAS, `clock-drawing' and SPECT, 56 (84%) of the cases originally grouped together as well as 54 (81%) of the cross-validated grouped cases were correctly classi®ed by discriminant analysis. Brain atrophy does not always take place symmetrically [4,6]. Since, in a majority of the patients who grasped into the mirror, the focus of hypoperfusion in the SPECT was localised in the parieto-occipital regions [8,12], we concluded that these particular brain regions are crucial at this stage of DAT. This intermediate stage is connected with certain psychological testing parameters and can be distinguished from an earlier and a later phase of the illness [3,5,14]. Are our ®ndings comparable with those of Ramachandran et al. [13] and Binkofsky et al. [2]. All four patients of Ramachandran et al. [13] had left hemiplegia and hemianaesthesia, one also had hemianopia and another also had visual extinction. Of the ®ve patients described by Binkofsky et al. [2] as having `mirror agnosia' [1], only two suffered from paresis, and three of them from neurocognitive de®cits such as apraxia and neglect. In contrast to the patterns of neurological de®ciencies described by Ramachandran and Binkofsky, the DAT patients who grasped towards the mirror mainly showed neurocognitive but not clinical neurological disturbances like paresis or hypaesthesia. The ophthalmological tests also showed no pathological results. Are the phenomena described the result of a general

W. Massing et al. / Neuroscience Letters 299 (2001) 101±104

confusion in the DAT patients? Although the mean values of the ADAS and Benton tests differed signi®cantly between group 1 and group 2, the attention and concentration of the patients were not essentially impaired in either group. They understood the task completely and named the objects correctly. Their main cognitive de®ciency was a lack of memory. Consequently, grasping into a mirror is not a sign of general confusion but rather the result of a predominant focal disturbance of the brain. With regard to focal disturbances, especially in the parieto-occipital brain regions, DAT patients can be compared with the patients of Ramachandran et al. [13] and Binkofsky et al. [2]. But we have to assume that the local brain disturbances in the DAT patients are not so sharply distinct from the undestroyed brain tissue as in the cases described by Ramachandran et al. [13] and Binkofsky et al. [2]. The behaviour and the verbal utterances of the DAT patients during the investigation in front of the mirror showed some interesting-aspects. At the beginning of the investigation the patients correctly named the mirror as an object and explained its function. While some of the DAT patients, having been asked to take the object out of the investigator's hand, banged their hand directly against the mirror or reached behind it without comment, other patients hesitated and, just before the beginning of the experiment, expressed the impossibility of solving the given task. They said such things as `The bottle is inaccessible', `I cannot do this because there is a pane of glass in between', or `It doesn't work'. Only after being asked again did they try to reach into or behind the mirror. Despite being instructed several times, however, the patients did not change their behaviour but repeated their mistakes in the same and in the subsequent sessions. At a ®rst glance, it seems that we can describe the situation as in our former investigation: `the DAT patients were able to give a verbal de®nition of a mirror but were unable to transfer this declarative knowledge into procedural knowledge [11,15]. In spite of semantically understanding the concept of a mirror, they were unable to use the mirror as a tool. These ®ndings are similar to those of Hodges et al. [7]. In their patient FL, the semantic network had been preserved, whereas she was very impaired in mechanical problem-solving tasks'. But if we analyze the utterances of the DAT patients exactly, we have to conclude that they have a notion of a mirror which is different from that of the investigators. Admittedly, they name the mirror correctly and explain its functions; but then, after receiving the investigator's instructions and just before reacting, they develop ideas about the mirror's functions which do not accord with the abstract ideas they expressed previously. They are now convinced, for example, that the objects re¯ected in the mirror are in fact located behind it. The consternation of the investigator consists in the fact that his use of the word `mirror' differs from that of the DAT

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patients. He makes the tacit assumption that the word `mirror' has certain ®xed meanings, that mirror images are virtual, for example, or that there is `a perpendicular distance inversion' [9] which facilitates the ®nding of the real object. The reactions of the DAT patients show that the investigator is not able to comprehend all the meanings of the word `mirror'. The meaning of the word seems to be determined by the way the mirror is used [16]. Indeed the investigator conceives of the word `mirror' differently from the DAT patients, because his use of the mirror differs from theirs. In conclusion, the world of DAT patients, especially of those who try to reach into the mirror, is not the same as the investigator's. [1] Altschuler, E.L., Mirror agnosia: the Ramachandran sign [letter], Ann. Neurol, 47 (2000) 553±554. [2] Binkofski, F., Buccino, G., Dohle, C., Seitz, R.J. and Freund, H.J., Mirror agnosia and mirror ataxia constitute different parietal lobe disorders, Ann. Neurol., 46 (1999) 51±61. [3] Bondareff, W., Mountjoy, C.Q., Wischik, C.M., Hauser, D.L., LaBree, L.D. and Roth, M., Evidence of subtypes of Alzheimer's disease and implications for etiology, Arch. Gen. Psychiatry, 50 (1993) 350±356. [4] Brown, D.R., Hunter, R., Wyper, D.J., Patterson, J., Kelly, R.C., Montaldi, D. and McCullouch, J., Longitudinal changes in cognitive function and regional cerebral function in Alzheimer's disease: a SPECT blood ¯ow study, J. Psychiatr. Res., 30 (1996) 109±126. [5] DeKosky, S.T., Shih, W.J., Schmitt, F.A., Coupal, J. and Kirkpatrick, C., Assessing utility of single photon emission computed tomography (SPECT) scan in Alzheimer disease: correlation with cognitive severity, Alzheimer Dis. Assoc. Disord., 4 (1990) 14±23. [6] Goldenberg, G., Podreka, I., Suess, E. and Deecke, L., The cerebral localization of neuropsychological impairment in Alzheimer's disease: a SPECT study, J. Neurol., 236 (1989) 131±138. [7] Hodges, J.R., Spatt, J. and Patterson, K., `What' and `how': evidence for the dissociation of object knowledge and mechanical problem-solving skills in the human brain, Proc. Natl. Acad. Sci. USA, 96 (1999) 9444±9448. [8] Hof, P.R. and Bouras, C., Object recognition de®cit in Alzheimer's disease: possible disconnection of the occipito-temporal component of the visual system, Neurosci. Lett., 122 (1991) 53±56. [9] Hors®eld, E.C., Perception and a lateral inversion fallacy, Eur. J. Phys., 12 (1991) 207±209. [10] Maddox, J., The semantics of plane mirror inversion, Nature, 353 (1991) 791. [11] McCarthy, J. and Hayes, P.J., Some philosophical problems from the standpoint of arti®cial intelligence, In B. Mehler and D. Michie (Eds.), Machine Intelligence, Vol 4, Edinburgh University Press, Edinburgh, 1969. [12] Nitrini, R., Buchpiguel, C.A., Caramelli, P., Bahia, V.S., Mathias, S.C., Nascimento, C.M., Degenszajn, J. and Caixeta, L., SPECT in Alzheimer's disease: features associated with bilateral parietotemporal hypoperfusion, Acta Neurol. Scand., 101 (2000) 172±176. [13] Ramachandran, V.S., Altschuler, E.L. and Hillyer, S., Mirror agnosia, Proc. R. Soc. Lond. B, 264 (1997) 645±647. [14] Sabbagh, M.N., Lynn, P., Jhingran, S., Massman, P., Villanueva-Meyer, J., Olup, J. and Doody, R.S., Correlations between SPECT regional cerebral blood ¯ow and psycho-

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