SUBCORTICAL NEGLECT AS A CONSEQUENCE OF A REMOTE PARIETO-TEMPORAL DYSFUNCTION. A QUANTITATIVE EEG STUDY Catherine Colson1, Guy Demeurisse1, Claude Hublet1 and Jean-Louis Slachmuylder2 (1Service de Revalidation Neurologique, CHU Brugmann, Brussels, Belgium; 2Faculté des Sciences Psychologiques et de l’Education, Université Libre de Bruxelles, Brussels, Belgium)
ABSTRACT In patients with a right-sided deep-seated lesion, a causal relationship between a cortical dysfunction in the right temporo-parietal region and the occurrence of neglect has been suggested. In the present study we tried to correlate clinical and quantitative EEG data from a sample of 33 right stroke patients divided into two subgroups according to the presence or absence of neglect. A 20-channel EEG cartography system was used for EEG mapping. Delta and theta activities were calculated in sixteen regions of interest. The analysis of raw values stressed the importance of the right parieto-temporal cortex to discriminate between the two subgroups of patients. These results suggest that in patients with right subcortical damage, a remote cortical parieto-temporal dysfunction within an intra-hemispheric network is necessary to provoke neglect. Key words: neglect, diaschisis, subcortical lesion, quantitative EEG
INTRODUCTION There is evidence that in a number of patients with a deep-seated lesion sparing the cortex, a remote cortical dysfunction is present when cognitive disorders are observed. In right deep-seated lesions, the most frequently observed neuropsychological disorder is visuo-spatial neglect. In some studies using isotopic techniques, patients with left and right lesions were pooled and a separate analysis of the cortical dysfunction was not possible (Perani et al., 1987; Vallar et al., 1988; Baron et al., 1992). In other works, a causal relationship between a cortical dysfunction in the right temporo-parietal region and the occurrence of neglect has been suggested (Bogousslavsky et al., 1988; Perani et al., 1993; Bradvik et al., 1995; Hublet et al., 1995; Demeurisse et al., 1997). Quantified EEG (qEEG) is suitable to analyse brain functioning. Using this method in stroke patients with a right deep-seated lesion, preliminary results suggested that a right posterior dysfunction was associated with the occurrence of neglect (Demeurisse and Hublet, 1997; Demeurisse et al., 1998). We therefore decided to further study the pathophysiology of subcortical neglect by correlating clinical and qEEG data. MATERIALS
AND
METHODS
Subjects 33 stroke patients (20 men and 13 women) aged 25-88 years (mean 66), admitted to our department for stroke rehabilitation, were selected according to the following criteria: Cortex, (2001) 37, 619-625
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(a) Right-handedness assessed by the Edinburgh inventory. (b) No history of any previous neurological or psychiatric event. (c) CT and/or MRI evidence of a single deep-seated lesion in the right hemisphere, without cortical extension. (d) Absence of mental deterioration according to a standard neuropsychological investigation performed at the admission to our department (about 25 days after stroke onset) and including the following tests: time and place orientation, memory for contemporary events, auditory-verbal memory assessed with the Rey’s words test, general intellectual abilities assessed with the verbal part of the Wechsler Adult Intelligence Scale or with the Standard Progressive Matrices of Raven. Neglect was tested with the following tasks: I Letter cancellation task (LCT). II Copy of Rey’s Figure (CRF). III Albert’s cancellation task (shortened version) (ACT). IV Drawing from memory of a wheel (DW). V Zazzo’s cancellation task (shortened version) (ZCT). VI Line bisection task (LBT). VII Reading of compound words in which the right part is meaningfull alone (for example: cowboy) (RW). For each cancellation task, the scores were obtained by subtracting the number of targets detected on the left side from the number of targets detected on the right side. Consequently, any positive score corresponded to a lower performance on the left. For the line bisection task, the score was the number of millimeters deviation from the true center of the line, a positive score corresponding to a deviation towards the right and inversely. Normative values were previously obtained (Hublet et al., 1995). For these tests, any positive score ≥ 2.5 SD above the mean normal value was considered as pathological (i.e. higher or equal to 2.52 for LCT, 1.51 for ACT, 1.91 for ZCT and 5.4 for LBT). For the drawing tasks, omissions of details situated in the left side of the drawing were noted. For the reading task, failure to read left-sided letters was recorded. Apparatus and Procedure EEG Mapping System A 20-channel EEG cartography system (Beam-Nicolet Instruments Corporation) was used for EEG mapping. Twenty gold cup electrodes were placed on the head according to the 10/20 system. Linked-ears electrodes were used as reference. The electrode impedance was inferior to 3 kΩ. Analog filters of 1 to 300 Hz were used at amplifier. A 90 Hz antialiasing filter was placed after the amplifier. The sampling rate was 256 Hz. Artefact-free segments (at least 80 sec. length on the whole) were used to calculate absolute spectral amplitudes, using fast Fourier transform (FFT). The total spectral amplitude in the frequency range from 0.5 to 30 Hz was calculated for each electrode. Delta (1-3.5 Hz) and theta (4-7.5 Hz) activities (in µV) were calculated in sixteen regions of interest which are specified in Table II. Subjects were seated in a quiet dimly lit room. Recordings were made at rest about 35 days after stroke onset, with patients keeping their eyes closed Statistical Analysis Multivariate analysis of variance (MANOVA) is suitable to detect, among various ways of electrodes clustering, significant main effects and their interactions. The main effect (neglect or not neglect) defines two independent samples (between-subjects factor). Electrode locations on the hemisphere (locations) and laterality of the electrodes (hemisphere) effects define within-subjects factors. Their interactions with group main effect were of particular relevance to the present study. Five main effects and interactions have been tested, on delta and theta activities respectively: (1) Group main effect (all electrodes simultaneously, independently of the hemisphere and location effects). (2) Group by hemisphere interaction (all electrodes simultaneously and independently of the location effect). (3) Group by locations interaction (all locations simultaneously and independently of the hemisphere effect). (4) Group by hemisphere within location interaction. Processing all pairs of symmetrical locations simultaneously, measures the differential impacts of group effect on the eight locations of
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symmetrical couples. (5) Group by hemisphere interactions for individual pairs of symmetrical electrodes (each location separately in a specific design) indicating the differential impact of the group effect inside a specific symmetrical couple of electrodes.
RESULTS Sixteen patients out of 33 were diagnosed as affected by neglect. They correspond to the first 16 patients of Table I. The deep-seated injured structures (at CT and/or MRI) are reported in Table I. The internal capsule was lesioned in 75 % (12/16) of neglect patients (N+) vs. 59 % (10/17) of patients without neglect (N-). The centrum semiovale was lesioned in 88% (14/16) of N+ patients vs. in 76% (13/17) of N- patients. Either TABLE I
Demographic, Clinical and Radiological Data Clinical data Patient n°
Sex
Age
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33
M M M M M F M F F M M F F F F F M F M M M M M F F M M M M M F F M
65 54 51 57 61 72 71 70 68 59 64 81 64 61 79 74 25 64 69 58 62 64 64 74 69 64 88 67 59 65 86 74 61
Radiological data
LCT CRF ACT DW ZCT LBT RW 3 4 4 1 4 3 4 2 3 7 3 4 1 1 3 0 0 1 0 0 0 0 0 0 0 0 1 1 1 0 0 0 0
– – – + + + – + – + + + + – + + – – – – – – – – – – – – – – – – –
0 0 0 0 0 0 0 3 3 –3 23 1 1 0 14 3 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 –1 0
– – – – – – – – – – + – – – + – – – – – – – – – – – – – – – – –
5 1 4 0 3 2 2 3 0 11 10 1 1 3 5 3 –1 0 0 0 0 –1 1 0 0 0 –1 1 1 0 0 –1 0
1.5 0.7 5.5 2.0 3.0 3.0 2.0 –4.0 0 37.0 0.2 2.3 3.3 –0.4 0.5 5.5 –0.2 0.1 0.6 –0.1 0.3 0.7 2.3 1.0 –0.5 2.8 0 0 0 0 4.3 3.8 1.3
– – – – – – – – – + – – – – – – – – – – – – – – – – – – – – – – –
LN + + + +
CN
TH
+ +
+ + + + + +
+
+
IC
CSO
+ +
+ + + +
+ + + + + + + +
+
+ +
+
+
+ +
+
+ + + + + + +
+ + + + +
+ + + + + + + + + + + + + + + + + + +
+ +
+
+ + + +
Legend – Clinical data: LCT: letter cancellation task (neglect ≥ 2.52); CRF: copy of Rey’s figure (presence of neglect: +); ACT: Albert’s cancellation task (neglect: ≥ 1.51); DW: drawing from memory of a wheel (presence of neglect: +); ZCT: Zazzo’s cancellation task (neglect ≥ 1.91); LBT: line bisection task (neglect ≥ 5.4 mm); RW: reading of words (presence of neglect: +). Radiological data: IC: internal capsule (lesioned: +); LN: lenticular nucleus (lesioned: +); CN: caudate nucleus (lesioned: +); Th: thalamus (lesioned: +); CSO: centrum semiovale (lesioned: +). Abnormal results are printed in heavy types.
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internal capsule or centrum semiovale were injured in 100% of the cases, whether neglect was present or not. The lenticular nucleus was injured in 69% (11/16) of N+ patients as compared to 59% (10/17) in N- patients. In three N+ patients, the thalamus was also involved. qEEG A. Delta Activity Raw values are reported in Table II. Multivariate analysis of variance yielded the following findings: (1) Group main effect (computed on all electrodes simultaneously) was significant: F (1, 31) = 10.51, p = .003. (2) Group by hemisphere interaction (independently of the locations effect) was significant: F (1, 31) = 6.52, p = .016. (3) Group by locations interaction (independently of the hemisphere effect) was not significant: F (7, 25) = 1.81, p = .129. (4) Group by all pairs of symmetrical locations simultaneously (group by hemisphere within locations) interaction was significant: F (8, 24) = 3.34, p = .01, suggesting a large diversity of impacts of group effect among various locations of symmetrical electrodes. The group by hemisphere by locations interaction yielded an F (7, 25) = 2.43, p = .048. (5) Among the eight pairs of symmetrical electrodes, MANOVA contrasts displayed a significant group by hemisphere interaction for T5-T6 [F (1, 31) = 14.40, p = .001], and P3-P4 [F (1, 31) = 9.27, p = .005] and weaker levels of significance for C3-C4 [F (1, 31) = 5.64, p = .024] and T3-T4 [F (1, 31) = 6.04, p = .02]. B. Theta Activity Raw values are reported in Table II. Mutivariate analysis of variance yielded the following findings: (1) Group main effect (computed on all electrodes simultaneously) fell just short of the significance level: F (1, 31) = 3.30, p = .079. (2) Group by hemisphere interaction (independently of the locations effect) was significant: F (1, 31) = 8.07, p = .008. (3) Group by locations interaction (independently of the hemisphere effect) was not significant: F (7, 25) = 0.44, p = .865. (4) Group by all pairs of symmetrical electrodes simultaneously (group by hemisphere within locations) interaction was not significant F (8, 24) = 1.61, p = .174. The group by hemisphere by locations interaction yielded a F (7, 25) = 1.25, p = .315. (5) Among the eight pairs of symmetrical electrodes, MANOVA individual processings brought out significant group by hemisphere interactions for T5-T6 [F (1, 31) = 7.76, p = .009] and with a less marked significance for F3-F4 [F (1, 31) = 6.77, p = .014], and P3-P4 [F (1, 31) = 5.95, p = .021].
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TABLE II
Delta and Theta Activities: Raw Values ± SD (uV) of Patients without (N–) or with (N+) Neglect. Conventional Localization of the Electrodes According to the 10/20 System Delta Activity N–
Electrodes Fp1 Fp2 F7 F8 F3 F4 T3 T4 C3 C4 T5 T6 P3 P4 O1 O2
N+
Means
S.D
Means
S.D
59.23 59.60 36.10 41.92 38.21 40.54 24.56 25.08 31.61 31.64 26.46 25.79 30.91 30.92 28.78 29.44
26.67 25.03 12.79 14.59 10.59 12.59 7.03 7.12 8.79 8.36 7.32 8.21 8.28 10.15 10.39 11.86
66.82 67.99 48.29 54.45 49.86 55.38 36.87 44.42 45.39 51.36 36.03 44.05 43.68 51.27 39.14 42.83
20.20 22.04 13.08 20.98 11.94 19.24 13.14 20.79 14.41 17.75 13.69 13.55 13.87 16.77 15.23 14.64
Theta Activity N–
Electrodes Fp1 Fp2 F7 F8 F3 F4 T3 T4 C3 C4 T5 T6 P3 P4 O1 O2
N+
Means
S.D
Means
S.D
40.45 40.53 32.17 34.27 39.30 40.43 27.01 27.05 38.08 38.54 36.57 33.82 39.20 39.14 36.83 37.86
13.99 13.71 12.08 11.58 15.02 15.44 10.54 11.16 15.82 15.31 17.37 14.93 16.13 16.63 16.34 16.98
46.87 48.01 38.47 42.82 46.49 51.56 33.50 36.80 45.17 49.37 41.72 48.59 45.63 52.08 41.88 44.80
13.68 13.88 11.54 10.98 13.79 13.85 10.12 10.20 13.32 13.83 17.07 20.72 14.23 17.55 13.77 16.72
DISCUSSION As previously suggested, no difference in CT and/or MRI localization was observed between patients with and without neglect. The analysis of delta and theta activities raw values pointed out the importance of the right parieto-temporal associative cortex (T6, P4) and especially the right posterior temporal region (T6) to discriminate N+ from Npatients. This finding is in agreement with clinico-anatomical data. Spatial hemineglect has for a long time been described as a symptom with a remarkable localizing value, indicating a lesion in the parietal lobe (Brain, 1941). According to Critchley (1953), neglect was most often correlated with lesions in the
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posterior parietal and parieto-occipital regions. In patients undergoing a limited cortical ablation (for treatment of epilepsy), areas critical for the occurrence of neglect were the supramarginal and angular gyri and the posterior part of the 1st temporal gyrus (Hécaen et al., 1956). Further anatomo-clinical correlation studies confirmed that the most frequent correlate of neglect in humans was a retro-rolandic cortical lesion involving the temporo-parieto-occipital junction, especially the inferior parietal lobule (Vallar and Perani, 1986). When neglect was associated with subcortical damage, a cortical decrease in metabolism or cerebral blood flow remote from the deepseated lesion was observed in the right parieto-temporal region (Bogousslavsky et al., 1988; Perani et al., 1993; Hublet et al., 1995; Bradvik et al., 1995; Demeurisse et al., 1997). For Heilman et al. (1985), areas critical to provoke neglect are the inferior parietal lobule and the superior temporal sulcus which have been considered, as supramodal and polymodal association regions respectively, both areas being part of an intra-hemispheric network. In this model and in the model of Mesulam (1981), it has been suggested that also frontal regions contribute to the control of attention. Our results do not bring out an important frontal dysfunction, and simply emphasize the importance of the parieto-temporal dysfunction – remote from the morphological lesion – for the occurrence of hemispatial neglect. However, our neglect battery assessed peripersonal space only. A dissociation between neglect for “far” or “near” extrapersonal space has been observed in monkeys and in man. In monkeys, Rizzolatti et al. (1983) observed a more prominent neglect for objects in contralesional far space than in near space following unilateral ablation of the frontal eye field (area 8). By contrast, unilateral ablation of frontal area 6 (which receives direct projections from the inferior parietal lobule) results in inattention to visual stimuli limited to contralesional near space. In man, Halligan and Marshall (1991) described the case of patient T.M. who, after an unilateral right hemisphere stroke (within the territory of the middle cerebral artery, sparing the frontal cortex) showed severe left visuo-spatial neglect for peripersonal space only, neglect in far extrapersonal space being absent. REFERENCES BARON JC, LEVASSEUR M, MAZOYER B, LEGAULT-DEMARE F, MAUGUIERE F, PAPPATA S, JEDYNAK P, DEROME P, CAMBIER J, TRAN-DIHN S and CAMBON H. Thalamocortical diaschisis: Positron emission tomography in humans. Journal of Neurology, Neurosurgery and Psychiatry, 55: 935-942, 1992. BOGOUSSLAVSKY J, MIKLOSSY J, REGLI F, DERVAZ JP, ASSAL G and DELALOYE B. Subcortical neglect, neuropsychological, SPECT, and neuropathological correlations with anterior choroidal artery territory infarction. Annals of Neurology, 23: 448-452, 1988. BRADVIK B, SONESSON B, RYDING E and ROSEN I. Spatial and perceptual impairment related to cortical cerebral blood flow and EEG in deep white matter infarcts of the right hemisphere. European Neurology, 35: 80-85, 1995. BRAIN WR. Visual disorientation with special reference to lesions in the right cerebral hemisphere. Brain, 64: 244-272, 1941. CRITCHLEY M. The Parietal Lobes. London: Edward Arnold and Co., 1953. DEMEURISSE G and HUBLET C. Correlative study of quantified EEG and neglect in right-sided subcortical stroke. European Journal of Neurology, 4: supp. 1, 562, 1997. DEMEURISSE G, HUBLET C and PATERNOT J. Quantitative EEG in subcortical neglect. Clinical Neurophysiology, 28: 259-265, 1998. DEMEURISSE G, HUBLET C, PATERNOT J, COLSON C and SERNICLAES W. Pathogenesis of subcortical visuo-spatial neglect. A HMPAO SPECT study. Neuropsychologia, 35: 731-735, 1997.
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HALLIGAN PW and MARSHALL JC. Left neglect for near but not far space in man. Nature, 350: 498-500, 1991. HÉCAEN H, PENFIELD W, BERTRAND C and MALMO R. The syndrome of apractognosia due to lesions of the minor cerebral hemisphere. Archives of Neurology and Psychiatry, 75: 400-434, 1956. HEILMAN K, WATSON R and VALENSTEIN E. Neglect and related disorders. In K Heilman and E Valenstein (Eds.), Clinical Neuropsychology (2nd ed.). New York-Oxford: Oxford University Press, 1985. HUBLET C, DEMEURISSE G, PATERNOT J, COLSON C and CAPON A. Remote cortical dysfunction as a possible cause of subcortical neglect. European Neurology, 35: 254-258, 1995. MESULAM MM. A cortical network for directed attention and unilateral neglect. Annals of Neurology, 10: 309-325, 1981. PERANI D, VALLAR G, CAPPA S, MESSA C and FAZIO F. Aphasia and neglect after subcortical stroke. A clinical cerebral perfusion correlation study. Brain, 110: 1211-1229, 1987. PERANI D, VALLAR G, PAULESU E, ALBERONI M and FAZIO F. Left and right hemisphere contribution to recovery from neglect after right hemisphere damage. An (18F) FDG PET study of two cases. Neuropsychologia, 31: 115-125, 1993. RIZZOLATTI G, MATELLI M and PAVESI G. Deficits in attention and movement following the removal of postarcuate (area 6) and prearcuate (area 8) in macaque monkeys. Brain, 106: 665-673, 1983. VALLAR G and PERANI D. The anatomy of unilateral neglect after right hemisphere stroke lesions. A clinical / CT scan correlation study in man. Neuropsychologia, 24: 609-622, 1986. VALLAR G, PERANI D, CAPPA S, MESSA C, LENZI GL and FAZIO F. Recovery from aphasia and neglect after subcortical stroke: neuropsychological and cerebral perfusion study. Journal of Neurology, Neurosurgery and Psychiatry, 51: 1269-1276, 1988. Catherine Colson, Service de Revalidation Neurologique, CHU Brugmann, Place A. Van Gehuchten, 4, B, 1020 Brussels, Belgium. Email:
[email protected]
(Received 20 July 2000; reviewed 6 April 2001; revised 2 May 2001; accepted 3 May 2001)
