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Awareness of intending to act following parietal cortex resection
Neuropsychologia 46 (2008) 2662–2667
Contents lists available at ScienceDirect
Neuropsychologia journal homepage: www.elsevier.com/locate/neuropsychologia
Awareness of intending to act following parietal cortex resection Gilles Lafargue a,∗ , Hugues Duffau b a b
Laboratoire Neurosciences Fonctionnelles & Pathologies, CNRS, Universit´e Lille Nord-de-France, France D´epartement de neurochirurgie, CNRS FRE 2987, hˆ opital Gui-de-Chauliac, CHU de Montpellier, France
a r t i c l e
i n f o
Article history: Received 13 January 2008 Received in revised form 27 April 2008 Accepted 28 April 2008 Available online 3 May 2008 Keywords: Functional neuroplasticity Conscious will Motor intention
a b s t r a c t Neuroimaging and neuropsychological studies have provided evidence suggesting that the inferior parietal lobule (IPL) plays a crucial role in the awareness of motor intentions. For instance, patients with IPL lesions caused by stroke selectively differ in the temporal judgements of their intentions to move compared with healthy controls [Sirigu, A., Daprati, E., Ciancia, S., Giraux, P., Nighoghossian, N., Posada, A., et al. (2004). Altered awareness of voluntary action after damage to the parietal cortex. Nature Neuroscience, 7(1), 80–84]: they experience the will to move only at the moment they start moving, and not before, as it should normally be the case. In the study presented here, we failed to replicate the main behavioral findings of the study quoted above in three patients with surgical resection of the right IPL following slow-growing lesions. Their performances contrasted with that of stroke patients. The timing of their intentions to act but also the delay between their judgements of intention and movement onsets were in the normal range of values for matched controls, when tested with the temporal judgement task developed by Benjamin Libet. There are in the literature some reported cases of functional neuroplasticity following surgical resection of large amount of cerebral tissue. This mainly concerns the brain regions underpinning language and primary sensorimotor functions. Because of the small number of patients our data must be regarded cautiously. They provide preliminary behavioral support to extend to conscious awareness of willing the functional neuroplasticity potentialities of the brain, in human adults. A new perspective towards a hodological view for higher-order cognitive processes seems open. © 2008 Elsevier Ltd. All rights reserved.
1. Introduction The inferior parietal lobe (IPL) is supposed to play a crucial role in various aspects of the awareness of willed action and the experience of agency (Farrer & Frith, 2002; Farrer et al., 2008; Mattingley, Husain, Rorden, Kennard, & Driver, 1998; Sirigu et al., 1996, 2004). For instance, patients with IPL lesions caused by strokes have difficulties in mentally simulating motor acts (Sirigu et al., 1996) and have lost the ability to correctly estimate the moment in time when their intention to act is defined (Sirigu et al., 2004). Abnormal IPL activation has been observed in patients suffering from schizophrenia when these patients feel their actions as controlled by alien forces (Spence et al., 1997). When healthy subjects do not feel in control of their actions following experimental visual distortions, an abnormal activity in the IPL has also been observed (Farrer & Frith, 2002). In the study reported here we have investigated the performance in the Libet et al.’s task (Libet, Gleason, Wright, & Pearl, 1983) in three patients with surgical resection of the right IPL following
∗ Corresponding author. Tel.: +33 3 20 41 63 69; fax: +33 3 20 41 60 32. E-mail address: [email protected] (G. Lafargue). 0028-3932/$ – see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropsychologia.2008.04.019
low-grade glioma (LGG). Their performances have been compared to that of twelve matched healthy subjects. Participants, in the Libet’s paradigm, have to press a button at a chosen moment of their own free selection while watching a hand moving round a clock face. They then have to report – depending on experimental conditions – the time at which they first became aware of their intention (or will) to move (W-judgement) or the time at which they became aware of moving their finger (M-judgement). In this paradigm, the estimated position of the hand allows to date the subjective occurrence of both events. In healthy subjects, as reported consistently by several studies, the awareness of the intention to move occurs roughly in average −200 ms (between −239 and −141 ms) before the movement itself (Brass & Haggard, 2007; Haggard & Eimer, 1999; Keller & Heckhausen, 1990; Lau, Rogers, Haggard, & Passingham, 2004; Libet et al., 1983; Sirigu et al., 2004). As mentioned above, patients with acute IPL lesions show abnormalities in the awareness of their intentions. When tested with the Libet’s paradigm, contrary to patients with cerebellar lesions and healthy subjects, they cannot differentiate W-judgement from Mjudgement (Sirigu et al., 2004). In other words, they become aware of their intention to move at the time they start moving. Interestingly, neuroimaging data show an increase of activity in pre-SMA,
G. Lafargue, H. Duffau / Neuropsychologia 46 (2008) 2662–2667
dorsolateral prefrontal cortex and IPL when healthy subjects attend to their intention to move (Lau et al., 2004), confirming the crucial role of fronto-parietal networks in the awareness of voluntary action. Whereas the cerebellum would hold internal models related to the automatic control of movement (Wolpert, Ghahramani, & Jordan, 1995), it has been suggested that the parietal cortex holds internal models related to the awareness of movement and intention (Blakemore & Sirigu, 2003; Desmurget & Grafton, 2000). If so, we might expect that patients with resection of the IPL should be drastically impaired in tasks involving conscious awareness of one’s own motor intentions. Since the very influential works by Broca and Wernicke in the nineteenth century, the dominant view in cognitive neuroscience considers the brain as organized into highly specialized structures, the so-called “eloquent” regions. Until today it has been largely believed that a lesion within an eloquent area gives rise to major irrevocable and specific deficits. The finding that the brain is organized into highly specialized functional modules is challenged by the description of cases of considerable functional remapping following lesions. For instance, several studies have shown no significant decline in overall intellectual performance after hemispherectomy, the removal of one hemi-
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sphere of the brain (Delvin, Cross, & Harkness, 2003; Lindsay, Glaser, Richards, & Ounsted, 1984; McFie, 1961) performed on children with refractory epilepsy. However, it was believed that compensatory reorganization in brain-injured children could only occur early in life. The traditional view of neuroplasticity is now questioned by a growing body of data showing that, in the context of a slow tumoral invasion, surgical resection of a large amount of cerebral tissue could be performed, on adults, without any identified functional consequences. Moreover, very shortly after the resection, patients seem to have a normal social and professional life (Desmurget, Bonnetblanc, & Duffau, 2007). Such functional plasticity has been observed after surgical resection of LGG located in language and primary sensorimotor regions (Duffau, 2005). While reassuring, these findings do not exclude the possibility of subtle deficits only detectable with laboratory tasks. In addition, it is not known whether functional plasticity is extendable to all brain functions. In the present study, using a classical laboratory task, we examined whether the functional compensation potentialities of the brain are extendable to networks involved in the conscious experience of intending to act.
Fig. 1. Post-operative anatomical MRI of the patients confirms the resection of right IPL in the three patients.
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2. Methods 2.1. Subjects Twelve healthy adult volunteers (8 right-handed females and 4 left-handed males) and 3 patients (2 right-handed females and 1 left-handed male) with surgical resection of the right IPL invaded by a WHO grade II glioma took part in the study. The resections included the angular gyrus (Brodmann area 39) that was the damaged cortical region common to all five parietal patients of the Sirigu et al. study (2004). Each patient was matched by age, laterality and educational level to four healthy subjects. 2.1.1. Description of the cases (see Fig. 1 for post-operative individual MRI) 2.1.1.1. Case 1. NC was a right-handed married woman (38-year old at the time of testing) with three children, who worked as a teacher. She had a low-grade (WHO grade II) glioma localized into the right IPL and the somatosensory areas, which were resected 8 months previously. She performed normally on basic sensory and neuropsychological testing. According to her, she had completely recovered and enjoyed a normal social life. However, about twice a week she suffered from partial epilepsy episodes (about 1 min long) with dysesthesia in her left face and arm. For this reason, she cannot drive and then cannot resume her normal professional life at the time of testing (Fig. 1). 2.1.1.2. Case 2. Patient SB was a left-handed man (aged 30 at the time of investigation) who worked as an electrician and raised alone his 3-year-old child. He had a low-grade (WHO grade II) glioma within the right supramarginalis gyrus infiltrating the whole angular gyrus, which was resected 2 years previously. According to him, he felt completely recovered and had a normal social and professional life. He performed normally to a wide range of clinical sensory and neurocognitive testing and had resumed his normal professional life. 2.1.1.3. Case 3. MF was a 31-year-old right-handed married woman with two children, who worked as a cashier in a supermarket. She had a low-grade (WHO grade II) glioma infiltrating into the whole right IPL, which was resected 4 months previously. According to her reports, she was completely recovered, except for a slight sensory deficit at the extremity of the fingers of her left hand with no consequences in everyday life. She performed normally to a wide range of basic clinical sensory and neurocognitive testing and had resumed her normal professional life. Examination of post-operative brain MRI confirms the resection of right IPL in the three patients, with the removal of the angular gyrus (Fig. 1). This was associated to a resection of the supramarginalis gyrus (its posterior part in SB, entirely in the two other patients) in addition to a part of the retrocentral gyrus in MF.
clock’s hand had completed its first full revolution. In the “Movement” condition, subjects were instructed to attend to the actual onset of their finger movement and report the location of the clock’s hand when they executed the movement (M-judgement). In the “Intention” condition (analogous of the W-judgement of Libet, for “wanting” or “will” to move), they were asked to report the location of the clock’s hand when they first made their internal decision to move. In this latter condition the instruction was phrased as follows: “Note the position of the clock’s hand at the time when you first felt the will to press the key.” After the spacebar was pressed, the clock’s hand disappeared after a variable period (1200–3600 ms). Depending on the blocks, subjects executed the task with their right or left index finger. After some familiarization trials, each subject performed 8 blocks of 20 trials: 2 W-judgement blocks and 2 M-judgement blocks for each hand. All the participants performed the first half of the experiment with their left hand, which was the contralesional hand for the patients. For each hand the 4 20-trials blocks were organized with an order of either Movement–Intention–Intention–Movement (patients MF and SB and half of the controls) or Intention–Movement–Movement–Intention (patient NC and the other half of the controls). Between blocks there was a 3-min rest period. In order to check whether a possible deficit in W-judgement or M-judgement could not result from a nonspecific impairment in making correct temporal estimations, in a second task we assessed the subjects’ ability to make temporal estimation of the onset of a sound delivered by the computer (S-judgement). 3.2. Data recording
3. Procedure
For each trial, the time the spacebar press actually occurred was subtracted from the time that subjects reported they executed (M-judgement) or first intended to execute the movement (W-judgement). For the control task (S-judgement), the time when the sound actually occurred (as recorded by the computer) was subtracted from the time subjects reported hearing the sound. A negative value indicates that the subject’s estimate preceded the real event; a positive value indicates that it followed the real event.
3.1. Experimental tasks
3.3. Data analysis
Subjects sat in front of a computer 40 cm away from the screen. Their index finger was on the spacebar. A clock with a single hand appeared at the center of the screen (Fig. 2). At the beginning of each trial, the clock’s hand started to move clockwise from a random location and completed a revolution in 2.56 s. Subjects were asked to press the spacebar with their index finger at a time of their own choosing: they were told to feel free to execute the movement whenever they wanted, but not before the
We first examined W-judgement and M-judgement in the control group. A two-way ANOVA with repeated measures on Required Judgement and Hand as within subject factors was performed. Then the performances of NC, SB and MF were independently compared to that of the control group. Note that each patient was compared to the whole sample of controls because a preliminary analysis did not reveal any effects of gender, educational level, laterality and category of age in our task. The patients’ performances were evaluated by using Crawford and Howell’s modified t tests for comparing single cases to small control samples (Crawford & Howell, 1998). This method (Crawford & Garthwaite, 2002; Crawford & Howell, 1998) (i) addresses the question of whether or not a patient exhibits a statistically significant deficit and (ii) provides a point estimate of the abnormality of the score, i.e. it estimates the percentage of the control population that would obtain a score lower than the patient. Thus, we checked whether each patient was significantly different from controls on W-judgement and M-judgement, and whether her/his delay between both events was significantly different from controls. We also assessed the estimation of the onset of a sound first for control subjects and then for patients, as previously. We used the modified t-test to check whether the estimation given by each patient fell inside or outside the confidence interval of the mean value of the control sample.
Fig. 2. Time course of the task. At time 0 the clock appeared and the hand began to rotate. Each revolution was completed in 2.56 s. Subjects were asked to press the spacebar with their index finger at a time of their own choosing. Depending on the experimental condition, they then had to report the position of the clock’s hand either when they felt the intention to move (W-judgement) or when they actually started moving (M-judgement). The subjects were instructed to let the urge to act appear on its own at any time without any preplanning or concentration on when to act.
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4.2. Patients For both hands, when individually compared with the control sample, the patients’ judgements fell inside the confidence intervals of the control mean values for W-judgement and M-judgement. For each patient, the differences between both events also fell inside the confidence intervals of the control mean value. Patients’ performances (left contralesional hand) are presented in Fig. 3B. Outputs of Crawford and Howell’s modified t tests are presented in Table 1. 4.3. Temporal estimation of the onset of a sound Patients and controls’ abilities to make temporal estimation of the onset of a sound were not significantly different. Among the patients and the control group the estimates preceded, in average, the time when the sound actually occurred as already observed in the literature. 5. Discussion
Fig. 3. Results (mean and standard deviations) for W-judgement and M-judgement in control subjects (A) and mean value for the three patients with inferior parietal resection following low-grade glioma (B). Each bar represents the difference in ms between subjective report and the exact time of key press. Note that we present here the results for the task performed with the left hands, which were the patients’ contralesional hands.
4. Results 4.1. Healthy subjects On average healthy subjects estimated the time they intended to move (W-judgement) before (−191 ± 65 ms) the actual movement onset. They also estimated the time they started to move (Mjudgement) on average before (−51 ± 43 ms) the actual movement onset. The difference between both estimations was statistically significant [F(1, 11) = 95.21; p < 0.0001]. None of the other main (Hand) and interaction (Hand × Required Judgement) effects reached statistical significance. Healthy subjects’ performances (left hand) are presented in Fig. 3A.
The current study was designed to investigate the impact of parietal cortex resection on the ability to attend to motor intentions. Attention to intention may be “one mechanism by which effective conscious control of action becomes possible” (Lau et al., 2004). A recent study by Farrer et al. (2008) showed that the right angular gyrus – a part of the IPL, which was completely resected in the patients of the present study – is specifically activated in conditions where healthy subjects intend to consciously access to different aspects of one’s own actions. This finding reinforces the hypothesis that the IPL is involved in the conscious monitoring of intention. We examined the performance of three patients with surgical resection of the right IPL in the temporal judgement task developed by Benjamin Libet (Libet et al., 1983). When compared to the mean of healthy subjects judgements, our patients tended to give delayed judgements for both W-judgement and M-judgement. However, their performances were inside the confidence interval of the normative sample for both conditions. For each patient, the delay between W-judgement and M-judgement was also inside the confidence interval of the normative sample. Such a pattern contrasts with the performance of patients with IPL lesions caused by strokes. Using the same paradigm as ours, Sirigu et al. (2004) have showed that patients with IPL lesions caused by strokes could not distinguish between the onsets of intentions and movements when they performed the task with their contralesional hand. Contrary to our patients, the patients of this study had lost the ability to feel their will to act that is the sense of being about to move. Interestingly, readiness potential (RP) – an electrophysiological mark of motor preparation recorded on the scalp over motor areas – was
Table 1 Outputs of Crawford and Howell’s modified t tests (Crawford & Garthwaite, 2002; Crawford & Howell, 1998) in patients NC, SB and MF versus healthy participants, for the left hand NC
SB
MF
Modified t-test on difference between the patient’s estimation and the mean estimation of the control group for M (two-tailed)
t = 0.20 p = 0.84
t = 0.56 p = 0.59
t = 1.41 p = 0.19
Modified t-test on difference between the patient’s estimation and the mean estimation of the control group for W (one-tailed)
t = 1.05 p = 0.16
t = 0.47 p = 0.32
t = 0.87 p = 0.20
Estimated percentage of normal population experiencing the will to move later than the patient (%)
15.82
32.27
20.09
Modified t-test comparing the patient and the control group for the delays between times W and M (two-tailed)
t = −1.06 p = 0.31
t = −0.12 p = 0.91
t = 0.07 p = 0.95
Estimated percentage of normal population with a delay between times W and M shorter than the patient (%)
15.51
45.33
52.67
The tests were performed with the program SINGLIMS.exe. All the patients were in the normal range for M-judgement, W-judgement, and the delay between both events.
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poorly detectable in these patients during W-judgement, contrary to healthy matched subjects and cerebellar patients. Unfortunately we did not measure RP in our study and therefore we cannot provide a physiological marker of reorganization of intention monitoring in patients with IPL resection. It would have been interesting to know if our patients had normal or close to normal RP. Without measure of RP, a criticism of our behavioral finding could be to point out the fact that we could not reject a null effect and that this null effect was in the direction of that found by Sirigu et al. (2004). Then, one could argue that if we had included enough patients in our study the delay in W might have been statistically different from controls. This is a possible interpretation of our results. However, if mean W judgements were delayed in our patients, all judged their intention to arise before their movements and, once again, all were in the normal range of values for healthy matched subjects. Consequently, with more patients with IPL resection that is with a fully powered study we cannot exclude the possibility that patients’ W times would be significantly later than the average of healthy matched controls. However, we can speculate with some confidence that the pattern of performance of patients with IPL resection would be much closer to that of healthy subjects than to that of parietal patients. Altogether these claims support the hypothesis that the conscious experience of intending to act can be, at least, partially compensated following brain damage. To reinforce our view it is of interest to note that beyond a certain threshold an abnormal experience of the will to move should be associated with an impaired sense of volition, leading to clinical symptoms. As already mentioned, most of the patients with IPL resection following LGG do not have symptoms related to willed actions, as apraxia, detectable at a clinical level. Moreover, only few months after surgery, most of these patients enjoy a normal social and professional life. Except for slight sensory deficit in some cases at the beginning of their recovery, they feel completely normal. A likely explanation of the performance of our patients – and of the difference between both studies – is that slow-evolving glioma and surgical resection can trigger major neural reorganizations, with new brain structures taking over the functions of the lost neural tissue (Desmurget et al., 2007). WHO grade II glioma is a slow-growing tumor. Its temporal course was estimated using biomathematical models, with an average slope of 4.1 mm per year (Mandonnet et al., 2003). This data is very important, since it has been demonstrated that the mechanisms of cerebral plasticity, especially the recruitment of remote brain areas in the ipsi- and contralesional hemispheres, is much more efficient in slow growing than acute lesions (Desmurget et al., 2007). Therefore, such temporal pattern explains why functional recovery is considerably better in the context of WHO grade II glioma than after a stroke. Hence, a hypothesized cognitive function of the IPL, namely its implication in the conscious experience of motor intentions, might be moved towards other brain networks or other brain structures involved in the network when it is infiltrated by a slow-growing lesion such as a LGG. Future studies will have to map out functional neural reorganization in patients with LGG localized in the IPL, before and after surgical resection of this structure. Except for a seizure in one case, our patients did not report any sensorimotor deficits or cognitive complaints before surgery, which might mean that their slow-growing lesions had triggered major preoperative neural reorganizations. It will also be worth exploring whether the function is taken-over by an analogous system – not fully operative in healthy subjects – in the contralateral hemisphere or/and whether the compensation involves perilesional adjacent areas and distant ipsilateral cerebral regions. All the patients presented here were operated under local anesthesia and could benefit from online cortical and subcortical sensorimotor mapping, so as
to preserve the eloquent structures around the tumor and the anatomo-functional integrity of white fibers. This latter point could be crucial to account for the better functional recovery in patients with LGG compared to patients with lesions caused by strokes. Indeed, acute brain destructions could cause undetected damages in the perilesional tissue and generally does not preserve the white matter tracts (Desmurget et al., 2007). On the basis of in vitro studies, animal experimentations and human data, pathophysiological mechanisms underlying functionnal reorganization in patients with LGG have recently been reviewed as follows: (i) modulations of synaptic efficacy, unmasking of latent connections, changes of synchrony, glial modulation, phenotypic modifications and neurogenesis have been identified at a microscopical level; (ii) resolution of diaschisis, functional redundancies within large-scale networks, sensory substitution (cross-modal plasticity) and morphological changes have been described at a macroscopical level (Duffau, 2006, 2008a). In brief, our study suggests that the conscious experience of intending to act can be at least partially compensated following brain damage in adults. As already suggested for language (Duffau, 2008a,b), this original finding might open a new door towards a hodological view – and then a high potential of cerebral plasticity – for higher-order cognitive functions. Conflict of interest The authors declare that they have no conflict of interest. Acknowledgements We thank Mathilde Martin and Jeanne Toulouse for their English corrections. We also thank two anonymous reviewers for their useful comments. GL was supported by the Agence Nationale pour la Recherche “Neurosciences Neurology et Psychiatrie”, the European Science Fundation “Conciousness in Natural and Cultural Context” and the BQR of Lille III University. References Blakemore, S. J., & Sirigu, A. (2003). Action prediction in the cerebellum and in the parietal lobe. Experimental Brain Research, 153, 239–245. Brass, M., & Haggard, P. (2007). To do or not to do: The neural signature of self-control. Journal of Neuroscience, 27, 9141–9145. Crawford, J. R., & Howell, D. C. (1998). Comparing an individual’s test score against norms derived from small samples. The Clinical Neuropsychologist, 12, 482–486. Crawford, J. R., & Garthwaite, P. H. (2002). Investigation of the single case in neuropsychology: Confidence limits on the abnormality of test scores and test score differences. Neuropsychologia, 40, 1196–1208. Desmurget, M., & Grafton, S. (2000). Forward modeling allows feedback control for fast reaching movements. Trends in Cognitive Sciences, 4, 423. Desmurget, M., Bonnetblanc, F., & Duffau, H. (2007). Contrasting acute and slowgrowing lesions: A new door to brain plasticity. Brain, 130(Pt 4), 898–914. Devlin, A. M., Cross, J. H., Harkness, W., et al. (2003). Clinical outcomes of hemispherectomy for epilepsy in childhood and adolescence. Brain, 126, 556–566. Duffau, H. (2005). Lessons from brain mapping in surgery for low-grade glioma: Insights into associations between tumour and brain plasticity. Lancet Neurology, 4, 476–486. Duffau, H. (2006). Brain plasticity: From pathophysiological mechanisms to therapeutic applications. Journal of Clinical Neuroscience, 13(9), 885–897. Duffau, H. (2008a). Brain plasticity and tumors. Advances in Technical Neurosurgery, 33, 3–33. Duffau, H. (2008b). The anatomo-functional connectivity of language revisited new insights provided by electrostimulation and tractography. Neuropsychologia, 46(4), 927–934. Farrer, C., & Frith, C. (2002). Experiencing oneself vs. another person as being the cause of an action: The neural correlates of the experience of agency. Neuroimage, 15(3), 596–603. Farrer, C., Frey, S. H., Van Horn, J. D., Tunik, E., Turk, D., Inati, S., et al. (2008). The angular gyrus computes action awareness representations. Cerebral Cortex, 18, 254–261. Haggard, P., & Eimer, M. (1999). On the relation between brain potentials and the awareness of voluntary movements. Experimental Brain Research, 126, 128– 133.
G. Lafargue, H. Duffau / Neuropsychologia 46 (2008) 2662–2667 Keller, I., & Heckhausen, H. (1990). Readiness potentials preceding spontaneous motor acts: Voluntary vs. involuntary control. Electroencephalography and Clinical Neurophysiology, 76, 351–361. Lau, H. C., Rogers, R. D., Haggard, P., & Passingham, R. E. (2004). Attention to intention. Science, 303, 1208–1210. Libet, B., Gleason, C. A., Wright, E. W., & Pearl, D. K. (1983). Time of conscious intention to act in relation to onset of cerebral activity (readiness-potential)—The unconscious initiation of a freely voluntary act. Brain, 106, 623–642. Lindsay, J., Glaser, G., Richards, P., & Ounsted, C. (1984). Developmental aspects of focal epilepsies of childhood treated by neurosurgery. Developmental Medicine and Child Neurology, 26, 574–587. Mandonnet, E., Delattre, J. Y., Tanguy, M. L., Swanson, K. R., Carpentier, A. F., Duffau, H., et al. (2003). Continuous growth of mean tumor diameter in a subset of grade II gliomas. Annals of Neurology, 53, 524–528. Mattingley, J. B., Husain, M., Rorden, C., Kennard, C., & Driver, J. (1998). Motor role of human inferior parietal lobe revealed in unilateral neglect patients. Nature, 392(6672), 179–182.
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Neuropsychologia journal homepage: www.elsevier.com/locate/neuropsychologia
Awareness of intending to act following parietal cortex resection Gilles Lafargue a,∗ , Hugues Duffau b a b
Laboratoire Neurosciences Fonctionnelles & Pathologies, CNRS, Universit´e Lille Nord-de-France, France D´epartement de neurochirurgie, CNRS FRE 2987, hˆ opital Gui-de-Chauliac, CHU de Montpellier, France
a r t i c l e
i n f o
Article history: Received 13 January 2008 Received in revised form 27 April 2008 Accepted 28 April 2008 Available online 3 May 2008 Keywords: Functional neuroplasticity Conscious will Motor intention
a b s t r a c t Neuroimaging and neuropsychological studies have provided evidence suggesting that the inferior parietal lobule (IPL) plays a crucial role in the awareness of motor intentions. For instance, patients with IPL lesions caused by stroke selectively differ in the temporal judgements of their intentions to move compared with healthy controls [Sirigu, A., Daprati, E., Ciancia, S., Giraux, P., Nighoghossian, N., Posada, A., et al. (2004). Altered awareness of voluntary action after damage to the parietal cortex. Nature Neuroscience, 7(1), 80–84]: they experience the will to move only at the moment they start moving, and not before, as it should normally be the case. In the study presented here, we failed to replicate the main behavioral findings of the study quoted above in three patients with surgical resection of the right IPL following slow-growing lesions. Their performances contrasted with that of stroke patients. The timing of their intentions to act but also the delay between their judgements of intention and movement onsets were in the normal range of values for matched controls, when tested with the temporal judgement task developed by Benjamin Libet. There are in the literature some reported cases of functional neuroplasticity following surgical resection of large amount of cerebral tissue. This mainly concerns the brain regions underpinning language and primary sensorimotor functions. Because of the small number of patients our data must be regarded cautiously. They provide preliminary behavioral support to extend to conscious awareness of willing the functional neuroplasticity potentialities of the brain, in human adults. A new perspective towards a hodological view for higher-order cognitive processes seems open. © 2008 Elsevier Ltd. All rights reserved.
1. Introduction The inferior parietal lobe (IPL) is supposed to play a crucial role in various aspects of the awareness of willed action and the experience of agency (Farrer & Frith, 2002; Farrer et al., 2008; Mattingley, Husain, Rorden, Kennard, & Driver, 1998; Sirigu et al., 1996, 2004). For instance, patients with IPL lesions caused by strokes have difficulties in mentally simulating motor acts (Sirigu et al., 1996) and have lost the ability to correctly estimate the moment in time when their intention to act is defined (Sirigu et al., 2004). Abnormal IPL activation has been observed in patients suffering from schizophrenia when these patients feel their actions as controlled by alien forces (Spence et al., 1997). When healthy subjects do not feel in control of their actions following experimental visual distortions, an abnormal activity in the IPL has also been observed (Farrer & Frith, 2002). In the study reported here we have investigated the performance in the Libet et al.’s task (Libet, Gleason, Wright, & Pearl, 1983) in three patients with surgical resection of the right IPL following
∗ Corresponding author. Tel.: +33 3 20 41 63 69; fax: +33 3 20 41 60 32. E-mail address: [email protected] (G. Lafargue). 0028-3932/$ – see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropsychologia.2008.04.019
low-grade glioma (LGG). Their performances have been compared to that of twelve matched healthy subjects. Participants, in the Libet’s paradigm, have to press a button at a chosen moment of their own free selection while watching a hand moving round a clock face. They then have to report – depending on experimental conditions – the time at which they first became aware of their intention (or will) to move (W-judgement) or the time at which they became aware of moving their finger (M-judgement). In this paradigm, the estimated position of the hand allows to date the subjective occurrence of both events. In healthy subjects, as reported consistently by several studies, the awareness of the intention to move occurs roughly in average −200 ms (between −239 and −141 ms) before the movement itself (Brass & Haggard, 2007; Haggard & Eimer, 1999; Keller & Heckhausen, 1990; Lau, Rogers, Haggard, & Passingham, 2004; Libet et al., 1983; Sirigu et al., 2004). As mentioned above, patients with acute IPL lesions show abnormalities in the awareness of their intentions. When tested with the Libet’s paradigm, contrary to patients with cerebellar lesions and healthy subjects, they cannot differentiate W-judgement from Mjudgement (Sirigu et al., 2004). In other words, they become aware of their intention to move at the time they start moving. Interestingly, neuroimaging data show an increase of activity in pre-SMA,
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dorsolateral prefrontal cortex and IPL when healthy subjects attend to their intention to move (Lau et al., 2004), confirming the crucial role of fronto-parietal networks in the awareness of voluntary action. Whereas the cerebellum would hold internal models related to the automatic control of movement (Wolpert, Ghahramani, & Jordan, 1995), it has been suggested that the parietal cortex holds internal models related to the awareness of movement and intention (Blakemore & Sirigu, 2003; Desmurget & Grafton, 2000). If so, we might expect that patients with resection of the IPL should be drastically impaired in tasks involving conscious awareness of one’s own motor intentions. Since the very influential works by Broca and Wernicke in the nineteenth century, the dominant view in cognitive neuroscience considers the brain as organized into highly specialized structures, the so-called “eloquent” regions. Until today it has been largely believed that a lesion within an eloquent area gives rise to major irrevocable and specific deficits. The finding that the brain is organized into highly specialized functional modules is challenged by the description of cases of considerable functional remapping following lesions. For instance, several studies have shown no significant decline in overall intellectual performance after hemispherectomy, the removal of one hemi-
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sphere of the brain (Delvin, Cross, & Harkness, 2003; Lindsay, Glaser, Richards, & Ounsted, 1984; McFie, 1961) performed on children with refractory epilepsy. However, it was believed that compensatory reorganization in brain-injured children could only occur early in life. The traditional view of neuroplasticity is now questioned by a growing body of data showing that, in the context of a slow tumoral invasion, surgical resection of a large amount of cerebral tissue could be performed, on adults, without any identified functional consequences. Moreover, very shortly after the resection, patients seem to have a normal social and professional life (Desmurget, Bonnetblanc, & Duffau, 2007). Such functional plasticity has been observed after surgical resection of LGG located in language and primary sensorimotor regions (Duffau, 2005). While reassuring, these findings do not exclude the possibility of subtle deficits only detectable with laboratory tasks. In addition, it is not known whether functional plasticity is extendable to all brain functions. In the present study, using a classical laboratory task, we examined whether the functional compensation potentialities of the brain are extendable to networks involved in the conscious experience of intending to act.
Fig. 1. Post-operative anatomical MRI of the patients confirms the resection of right IPL in the three patients.
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2. Methods 2.1. Subjects Twelve healthy adult volunteers (8 right-handed females and 4 left-handed males) and 3 patients (2 right-handed females and 1 left-handed male) with surgical resection of the right IPL invaded by a WHO grade II glioma took part in the study. The resections included the angular gyrus (Brodmann area 39) that was the damaged cortical region common to all five parietal patients of the Sirigu et al. study (2004). Each patient was matched by age, laterality and educational level to four healthy subjects. 2.1.1. Description of the cases (see Fig. 1 for post-operative individual MRI) 2.1.1.1. Case 1. NC was a right-handed married woman (38-year old at the time of testing) with three children, who worked as a teacher. She had a low-grade (WHO grade II) glioma localized into the right IPL and the somatosensory areas, which were resected 8 months previously. She performed normally on basic sensory and neuropsychological testing. According to her, she had completely recovered and enjoyed a normal social life. However, about twice a week she suffered from partial epilepsy episodes (about 1 min long) with dysesthesia in her left face and arm. For this reason, she cannot drive and then cannot resume her normal professional life at the time of testing (Fig. 1). 2.1.1.2. Case 2. Patient SB was a left-handed man (aged 30 at the time of investigation) who worked as an electrician and raised alone his 3-year-old child. He had a low-grade (WHO grade II) glioma within the right supramarginalis gyrus infiltrating the whole angular gyrus, which was resected 2 years previously. According to him, he felt completely recovered and had a normal social and professional life. He performed normally to a wide range of clinical sensory and neurocognitive testing and had resumed his normal professional life. 2.1.1.3. Case 3. MF was a 31-year-old right-handed married woman with two children, who worked as a cashier in a supermarket. She had a low-grade (WHO grade II) glioma infiltrating into the whole right IPL, which was resected 4 months previously. According to her reports, she was completely recovered, except for a slight sensory deficit at the extremity of the fingers of her left hand with no consequences in everyday life. She performed normally to a wide range of basic clinical sensory and neurocognitive testing and had resumed her normal professional life. Examination of post-operative brain MRI confirms the resection of right IPL in the three patients, with the removal of the angular gyrus (Fig. 1). This was associated to a resection of the supramarginalis gyrus (its posterior part in SB, entirely in the two other patients) in addition to a part of the retrocentral gyrus in MF.
clock’s hand had completed its first full revolution. In the “Movement” condition, subjects were instructed to attend to the actual onset of their finger movement and report the location of the clock’s hand when they executed the movement (M-judgement). In the “Intention” condition (analogous of the W-judgement of Libet, for “wanting” or “will” to move), they were asked to report the location of the clock’s hand when they first made their internal decision to move. In this latter condition the instruction was phrased as follows: “Note the position of the clock’s hand at the time when you first felt the will to press the key.” After the spacebar was pressed, the clock’s hand disappeared after a variable period (1200–3600 ms). Depending on the blocks, subjects executed the task with their right or left index finger. After some familiarization trials, each subject performed 8 blocks of 20 trials: 2 W-judgement blocks and 2 M-judgement blocks for each hand. All the participants performed the first half of the experiment with their left hand, which was the contralesional hand for the patients. For each hand the 4 20-trials blocks were organized with an order of either Movement–Intention–Intention–Movement (patients MF and SB and half of the controls) or Intention–Movement–Movement–Intention (patient NC and the other half of the controls). Between blocks there was a 3-min rest period. In order to check whether a possible deficit in W-judgement or M-judgement could not result from a nonspecific impairment in making correct temporal estimations, in a second task we assessed the subjects’ ability to make temporal estimation of the onset of a sound delivered by the computer (S-judgement). 3.2. Data recording
3. Procedure
For each trial, the time the spacebar press actually occurred was subtracted from the time that subjects reported they executed (M-judgement) or first intended to execute the movement (W-judgement). For the control task (S-judgement), the time when the sound actually occurred (as recorded by the computer) was subtracted from the time subjects reported hearing the sound. A negative value indicates that the subject’s estimate preceded the real event; a positive value indicates that it followed the real event.
3.1. Experimental tasks
3.3. Data analysis
Subjects sat in front of a computer 40 cm away from the screen. Their index finger was on the spacebar. A clock with a single hand appeared at the center of the screen (Fig. 2). At the beginning of each trial, the clock’s hand started to move clockwise from a random location and completed a revolution in 2.56 s. Subjects were asked to press the spacebar with their index finger at a time of their own choosing: they were told to feel free to execute the movement whenever they wanted, but not before the
We first examined W-judgement and M-judgement in the control group. A two-way ANOVA with repeated measures on Required Judgement and Hand as within subject factors was performed. Then the performances of NC, SB and MF were independently compared to that of the control group. Note that each patient was compared to the whole sample of controls because a preliminary analysis did not reveal any effects of gender, educational level, laterality and category of age in our task. The patients’ performances were evaluated by using Crawford and Howell’s modified t tests for comparing single cases to small control samples (Crawford & Howell, 1998). This method (Crawford & Garthwaite, 2002; Crawford & Howell, 1998) (i) addresses the question of whether or not a patient exhibits a statistically significant deficit and (ii) provides a point estimate of the abnormality of the score, i.e. it estimates the percentage of the control population that would obtain a score lower than the patient. Thus, we checked whether each patient was significantly different from controls on W-judgement and M-judgement, and whether her/his delay between both events was significantly different from controls. We also assessed the estimation of the onset of a sound first for control subjects and then for patients, as previously. We used the modified t-test to check whether the estimation given by each patient fell inside or outside the confidence interval of the mean value of the control sample.
Fig. 2. Time course of the task. At time 0 the clock appeared and the hand began to rotate. Each revolution was completed in 2.56 s. Subjects were asked to press the spacebar with their index finger at a time of their own choosing. Depending on the experimental condition, they then had to report the position of the clock’s hand either when they felt the intention to move (W-judgement) or when they actually started moving (M-judgement). The subjects were instructed to let the urge to act appear on its own at any time without any preplanning or concentration on when to act.
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4.2. Patients For both hands, when individually compared with the control sample, the patients’ judgements fell inside the confidence intervals of the control mean values for W-judgement and M-judgement. For each patient, the differences between both events also fell inside the confidence intervals of the control mean value. Patients’ performances (left contralesional hand) are presented in Fig. 3B. Outputs of Crawford and Howell’s modified t tests are presented in Table 1. 4.3. Temporal estimation of the onset of a sound Patients and controls’ abilities to make temporal estimation of the onset of a sound were not significantly different. Among the patients and the control group the estimates preceded, in average, the time when the sound actually occurred as already observed in the literature. 5. Discussion
Fig. 3. Results (mean and standard deviations) for W-judgement and M-judgement in control subjects (A) and mean value for the three patients with inferior parietal resection following low-grade glioma (B). Each bar represents the difference in ms between subjective report and the exact time of key press. Note that we present here the results for the task performed with the left hands, which were the patients’ contralesional hands.
4. Results 4.1. Healthy subjects On average healthy subjects estimated the time they intended to move (W-judgement) before (−191 ± 65 ms) the actual movement onset. They also estimated the time they started to move (Mjudgement) on average before (−51 ± 43 ms) the actual movement onset. The difference between both estimations was statistically significant [F(1, 11) = 95.21; p < 0.0001]. None of the other main (Hand) and interaction (Hand × Required Judgement) effects reached statistical significance. Healthy subjects’ performances (left hand) are presented in Fig. 3A.
The current study was designed to investigate the impact of parietal cortex resection on the ability to attend to motor intentions. Attention to intention may be “one mechanism by which effective conscious control of action becomes possible” (Lau et al., 2004). A recent study by Farrer et al. (2008) showed that the right angular gyrus – a part of the IPL, which was completely resected in the patients of the present study – is specifically activated in conditions where healthy subjects intend to consciously access to different aspects of one’s own actions. This finding reinforces the hypothesis that the IPL is involved in the conscious monitoring of intention. We examined the performance of three patients with surgical resection of the right IPL in the temporal judgement task developed by Benjamin Libet (Libet et al., 1983). When compared to the mean of healthy subjects judgements, our patients tended to give delayed judgements for both W-judgement and M-judgement. However, their performances were inside the confidence interval of the normative sample for both conditions. For each patient, the delay between W-judgement and M-judgement was also inside the confidence interval of the normative sample. Such a pattern contrasts with the performance of patients with IPL lesions caused by strokes. Using the same paradigm as ours, Sirigu et al. (2004) have showed that patients with IPL lesions caused by strokes could not distinguish between the onsets of intentions and movements when they performed the task with their contralesional hand. Contrary to our patients, the patients of this study had lost the ability to feel their will to act that is the sense of being about to move. Interestingly, readiness potential (RP) – an electrophysiological mark of motor preparation recorded on the scalp over motor areas – was
Table 1 Outputs of Crawford and Howell’s modified t tests (Crawford & Garthwaite, 2002; Crawford & Howell, 1998) in patients NC, SB and MF versus healthy participants, for the left hand NC
SB
MF
Modified t-test on difference between the patient’s estimation and the mean estimation of the control group for M (two-tailed)
t = 0.20 p = 0.84
t = 0.56 p = 0.59
t = 1.41 p = 0.19
Modified t-test on difference between the patient’s estimation and the mean estimation of the control group for W (one-tailed)
t = 1.05 p = 0.16
t = 0.47 p = 0.32
t = 0.87 p = 0.20
Estimated percentage of normal population experiencing the will to move later than the patient (%)
15.82
32.27
20.09
Modified t-test comparing the patient and the control group for the delays between times W and M (two-tailed)
t = −1.06 p = 0.31
t = −0.12 p = 0.91
t = 0.07 p = 0.95
Estimated percentage of normal population with a delay between times W and M shorter than the patient (%)
15.51
45.33
52.67
The tests were performed with the program SINGLIMS.exe. All the patients were in the normal range for M-judgement, W-judgement, and the delay between both events.
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poorly detectable in these patients during W-judgement, contrary to healthy matched subjects and cerebellar patients. Unfortunately we did not measure RP in our study and therefore we cannot provide a physiological marker of reorganization of intention monitoring in patients with IPL resection. It would have been interesting to know if our patients had normal or close to normal RP. Without measure of RP, a criticism of our behavioral finding could be to point out the fact that we could not reject a null effect and that this null effect was in the direction of that found by Sirigu et al. (2004). Then, one could argue that if we had included enough patients in our study the delay in W might have been statistically different from controls. This is a possible interpretation of our results. However, if mean W judgements were delayed in our patients, all judged their intention to arise before their movements and, once again, all were in the normal range of values for healthy matched subjects. Consequently, with more patients with IPL resection that is with a fully powered study we cannot exclude the possibility that patients’ W times would be significantly later than the average of healthy matched controls. However, we can speculate with some confidence that the pattern of performance of patients with IPL resection would be much closer to that of healthy subjects than to that of parietal patients. Altogether these claims support the hypothesis that the conscious experience of intending to act can be, at least, partially compensated following brain damage. To reinforce our view it is of interest to note that beyond a certain threshold an abnormal experience of the will to move should be associated with an impaired sense of volition, leading to clinical symptoms. As already mentioned, most of the patients with IPL resection following LGG do not have symptoms related to willed actions, as apraxia, detectable at a clinical level. Moreover, only few months after surgery, most of these patients enjoy a normal social and professional life. Except for slight sensory deficit in some cases at the beginning of their recovery, they feel completely normal. A likely explanation of the performance of our patients – and of the difference between both studies – is that slow-evolving glioma and surgical resection can trigger major neural reorganizations, with new brain structures taking over the functions of the lost neural tissue (Desmurget et al., 2007). WHO grade II glioma is a slow-growing tumor. Its temporal course was estimated using biomathematical models, with an average slope of 4.1 mm per year (Mandonnet et al., 2003). This data is very important, since it has been demonstrated that the mechanisms of cerebral plasticity, especially the recruitment of remote brain areas in the ipsi- and contralesional hemispheres, is much more efficient in slow growing than acute lesions (Desmurget et al., 2007). Therefore, such temporal pattern explains why functional recovery is considerably better in the context of WHO grade II glioma than after a stroke. Hence, a hypothesized cognitive function of the IPL, namely its implication in the conscious experience of motor intentions, might be moved towards other brain networks or other brain structures involved in the network when it is infiltrated by a slow-growing lesion such as a LGG. Future studies will have to map out functional neural reorganization in patients with LGG localized in the IPL, before and after surgical resection of this structure. Except for a seizure in one case, our patients did not report any sensorimotor deficits or cognitive complaints before surgery, which might mean that their slow-growing lesions had triggered major preoperative neural reorganizations. It will also be worth exploring whether the function is taken-over by an analogous system – not fully operative in healthy subjects – in the contralateral hemisphere or/and whether the compensation involves perilesional adjacent areas and distant ipsilateral cerebral regions. All the patients presented here were operated under local anesthesia and could benefit from online cortical and subcortical sensorimotor mapping, so as
to preserve the eloquent structures around the tumor and the anatomo-functional integrity of white fibers. This latter point could be crucial to account for the better functional recovery in patients with LGG compared to patients with lesions caused by strokes. Indeed, acute brain destructions could cause undetected damages in the perilesional tissue and generally does not preserve the white matter tracts (Desmurget et al., 2007). On the basis of in vitro studies, animal experimentations and human data, pathophysiological mechanisms underlying functionnal reorganization in patients with LGG have recently been reviewed as follows: (i) modulations of synaptic efficacy, unmasking of latent connections, changes of synchrony, glial modulation, phenotypic modifications and neurogenesis have been identified at a microscopical level; (ii) resolution of diaschisis, functional redundancies within large-scale networks, sensory substitution (cross-modal plasticity) and morphological changes have been described at a macroscopical level (Duffau, 2006, 2008a). In brief, our study suggests that the conscious experience of intending to act can be at least partially compensated following brain damage in adults. As already suggested for language (Duffau, 2008a,b), this original finding might open a new door towards a hodological view – and then a high potential of cerebral plasticity – for higher-order cognitive functions. Conflict of interest The authors declare that they have no conflict of interest. Acknowledgements We thank Mathilde Martin and Jeanne Toulouse for their English corrections. We also thank two anonymous reviewers for their useful comments. GL was supported by the Agence Nationale pour la Recherche “Neurosciences Neurology et Psychiatrie”, the European Science Fundation “Conciousness in Natural and Cultural Context” and the BQR of Lille III University. References Blakemore, S. J., & Sirigu, A. (2003). Action prediction in the cerebellum and in the parietal lobe. Experimental Brain Research, 153, 239–245. Brass, M., & Haggard, P. (2007). To do or not to do: The neural signature of self-control. Journal of Neuroscience, 27, 9141–9145. Crawford, J. R., & Howell, D. C. (1998). Comparing an individual’s test score against norms derived from small samples. The Clinical Neuropsychologist, 12, 482–486. Crawford, J. R., & Garthwaite, P. H. (2002). Investigation of the single case in neuropsychology: Confidence limits on the abnormality of test scores and test score differences. Neuropsychologia, 40, 1196–1208. Desmurget, M., & Grafton, S. (2000). Forward modeling allows feedback control for fast reaching movements. Trends in Cognitive Sciences, 4, 423. Desmurget, M., Bonnetblanc, F., & Duffau, H. (2007). Contrasting acute and slowgrowing lesions: A new door to brain plasticity. Brain, 130(Pt 4), 898–914. Devlin, A. M., Cross, J. H., Harkness, W., et al. (2003). Clinical outcomes of hemispherectomy for epilepsy in childhood and adolescence. Brain, 126, 556–566. Duffau, H. (2005). Lessons from brain mapping in surgery for low-grade glioma: Insights into associations between tumour and brain plasticity. Lancet Neurology, 4, 476–486. Duffau, H. (2006). Brain plasticity: From pathophysiological mechanisms to therapeutic applications. Journal of Clinical Neuroscience, 13(9), 885–897. Duffau, H. (2008a). Brain plasticity and tumors. Advances in Technical Neurosurgery, 33, 3–33. Duffau, H. (2008b). The anatomo-functional connectivity of language revisited new insights provided by electrostimulation and tractography. Neuropsychologia, 46(4), 927–934. Farrer, C., & Frith, C. (2002). Experiencing oneself vs. another person as being the cause of an action: The neural correlates of the experience of agency. Neuroimage, 15(3), 596–603. Farrer, C., Frey, S. H., Van Horn, J. D., Tunik, E., Turk, D., Inati, S., et al. (2008). The angular gyrus computes action awareness representations. Cerebral Cortex, 18, 254–261. Haggard, P., & Eimer, M. (1999). On the relation between brain potentials and the awareness of voluntary movements. Experimental Brain Research, 126, 128– 133.
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