clin eeg neurosci 2007 machado 124 6

CLINICAL EEG and NEUROSCIENCE 02007 VOL. 38 NO. 3

Recognizing a Mother's Voice in the Persistent Vegetative State

C. Machado, J. Korein, E. Aubert, J. Bosch, M. A. Alvarez, R. Rodriguez, P. Valdes, L. Portela, M. Garcia, N. Perez, M. Chinchilla, Y. Machado and Y. Machado

Key Words

Consciousness Awareness Electroencephalography Gamma Coherence Persistent Vegetative State Quantitative Electric Tomography Vegetative State

ABSTRACT We studied an 8-year-old boy after a neardrowning left

him in a vegetative state (VS) for 4 years before the study. Findings fulfilled all clinical criteria for the diagnosis of VS. The purpose of this study was to investigate whether there was significant differential activation of the brain in response to hearing his mother's voice compared with the voices of unknown women. The data were assessed using quantitative electric tomography (QEEGt), a technique that combines anatomical information of the brain by MRI with EEG patterns to estimate the sources of the EEG within the brain. We found significant differences for EEG frequencies from 14-58 Hz, with a peak at 33.2 Hz (gamma band). The 3D reconstruction showed that these statistical differences were localized in the lateral and posterior regions of the left hemisphere. No significant differences were found between unknown women vs. basal conditions. These results demonstrate recognition of the mother's voice and indicate high-level residual linguistic processing in a patient meeting clinical criteria for VS. These findings launch new ethical and practical implications for the man- agement of VS patients.

INTRODUCTION The diagnosis of vegetative state (VS) has been made

more difficult by recognition of the minimally conscious state (MCS) as a transitional phase in the partial recovery of self-awareness or environmental awareness while emerging from the VS, leading to a relative high proportion of errors.' 5 Neuroimaging techniques have provided new insights for the pathophysiological elucidation of consciousness generation in these cases.267

The purpose of this study was to investigate whether there was significant differential activation of the patient's brain in response to hearing his mother's voice compared with the voices of unknown women.

MATERIALS AND METHODS We studied an 8-year-old boy after a near-drowning left

him in a VS for 4 years before the study. Findings fulfilled all clinical criteria for the diagnosis of VS. Diagnostic criteria for VS include: eye movements with lack of fixation, lack of evidence of awareness of self or environment, lack of interaction with others, and lack of comprehension or expression of language. Often stimuli result in massive stretching or startle reactions, without proper habituation, showing sometimes massive flexing responses. In our case, occasionally grimacing occurred after stimulation. Nonetheless, external stimuli did not evoke purposeful or sustained and reproducible voluntary behavioral responses. Hence, we definitely diagnosed our patient as a case of persistent vegetative state (PVS).a

The data were assessed using quantitative electric tomography (QEEGt), a technique that combines anatomical information of the brain by MRI with EEG patterns, to estimate the sources of the EEG within the brain.9-11

The EEG was recorded using nineteen monopolar der- ivations of the International 10-20 System (FPI, FP2, F3, F4, C3, C4, P3, P4,01 ,02 , F7, F8, T3, T4, T5, T6, Fz, Cz, Pz) with linked earlobes as a reference. Eye movement artifacts were monitored by use of the electrooculogram (EOG). The data acquisition was performed using a MEDI- CID-05 System (Neuronic S.A.). After visual editing to remove artifacts, 45 artifact-free samples were selected, each 2.5 seconds long, for each experimental condition, and were transformed using the FFT to the frequency domain, yielding a power spectrum from 0.78 to 70 Hz with a sampling frequency of 0.39 Hz (178 frequencies), with a 60 Hz notch filter.10

The Variable Resolution Electrical Tomography (VARE- TA) method was used for estimating EEG source genera-

From the Institute of Neurology and Neurosurgery, Cuba (C. Machado, M A Alvarez, L. Portela, M. Garcia, M Chinchilla, Y. Machado, Y Machado), Department of Neurology, New York University Medical Center, New York. USA (J Korein), Neuroscience Cuban Center (E. Aubert, J Bosch, P Valdes), and the International Center for Neurological Restoration. Cuba (R Rodriguez, N Perez).

Address requests for reprints to Calixto Machado, MD, PhD. Institute of Neurology and Neurosurgery, Apartado Postal 4268, Ctudad de La Habana 10400. Cuba.

Ernail: braind@inforned sld cu Received April 4, 2007, accepted April 11, 2007.

124 at Universidad Nacional Aut Mexic on March 15, 2015eeg.sagepub.comDownloaded from


Figure 1. a. Comparison of mother talks vs. basal record (red curve) showed significant differences in the EEG spectrum for frequencies from 14 to 56 Hz. with a peak at 32.2 Hz. No significant differences were found between unknown women vs. basal conditions (black curve). Axial QEEGt (Figure lb). and 3D maps (Figure lc), illustrate localization of activation in the left lateral and posterior region of the left hemisphere.

tors. Anatomical constraints were incorporated by using the patient's individual MRI. The MRI image was segmented to restrict the EEG sources to the gray matter within a grid of 3564 voxels. This technique is described elsewhere.9,11-'3

QEEGt was calculated in three experimental conditions lasting 5 minutes, at weekly intervals: basal record (no stimulus), listening to his mother's voice, and listening to 5 unknown women the same age as the mother who repeat- ed the same words as the mother. We used maternal expressions commonly used in the patient's daily life. Translated from Spanish to English the questions were: "My baby, mother is here, do you want to play with your doggy? He is here beside you." The study was conducted in the patient's room at home.

The power spectra of the EEGs recorded for the basal record, listening to his mother's voice, and listening to 5 unknown women were averaged to obtain a grand average spectrum for each electrode and for each experimental condition. These grand averages were used for the subse- quent analyses.

A Student's t-test was applied to assess significant differences for the EEG spectra between: "mother talks" vs. "basal," "unknown women talk" vs. "basal." The statistical significance threshold was corrected for Type I errors by using the multiplicity factor introduced by Worsely et al, based on the random field theory.14

RESULTS In Figure l a mother talks vs. basal conditions are com-

pared (red curve). Significant differences were found for EEG frequencies from 14 to 58 Hz, with a peak at 33.2 Hz (gamma band). No significant differences were found between unknown women vs. basal conditions (black curve). QEEGt maps, in the axial plane (Figure 1 b), and in a 3D reconstruction (Figure lc), showed that these statistical differences were localized in the lateral and posterior regions of the left hemisphere.

DISCUSSION Purhonen et all5 demonstrated that infants use more

attentional resources identifying the mother's voice than unfamiliar ones, whereas Maddock et a116 found that emotional words activated posterior cingulate cortex bilaterally, and that these regions may mediate interaction between emotional and memory related processes. In the neonatal period (birth to 28 days), an infant can already distinguish its mother's voice from that of other women. These behavioral features indicate a level of consciousness integration.1T-21

Di et a122 have recently evaluated the differences in brain activation using fMRl in response to presentation of the patient's own name spoken by a familiar voice in patients with VS and MCS. These authors found significant activation in primary auditory cortex in five of seven patients with VS emphasizing the "classic pattern" of dis- connected primary sensory cortex activation in patients with VS. Nonetheless, they were surprised with the finding of an atypical activation not only at the primary auditory cortex, but also in hierarchically higher order associative temporal areas in two VS cases. This activation pattern was also observed in all 4 patients with MCS. The activated areas included the right posterior of the superior temporal sulcus. These 2 VS patients recovered to an MCS, while the other 4 patients remained in VS.

Owen et a123.24 found residual cognitive functions indi- cating awareness in a persistent vegetative state patient (PVS) by MRI, even though all clinical diagnostic criteria of the VS were documented. They also noted that the comparison of speech with noise bursts revealed a significant increase of the rCBF on the superior part of the temporal plane bilaterally, and posterior to the auditory cortex in the



region of the planum temporale, in the left hemisphere only. They concluded that the observations provided com- pelling evidence for high-level residual linguistic processing in a patient with VS, and that some of the processes involved in activating, selecting and integrating contextual- ly appropriate word meanings may be intact in the PVS.

Nonetheless, for interpreting our resuits it is necessary to consider the time and space resolutions in assessing brain function comparing neurophysiologic with other neuroimaging methods. QEEGt directly reflects immediate neuronal activation, because this technique entails a high time resolution. Measurements made with fMRI, PET or SPECT are not only more indirect but require transport to

REFERENCES 1

2

3

4

5

6

7

8

9

10

11

12

Machado C. The minimally conscious state. definition and diagnostic criteria. Neurology 2002; 59: 1473-1474. Machado C. Cerebral processing in the minimally conscious state. Neurology 2005, 65: 973-974.

Machado C. Can vegetative state patients retain cortical processing? Clin Neurophysiol 2005, 116: 2253-2254. Machado C. Terminating artificial nutrition and hydration in persistent vegetative state patients: current and proposed state laws Neurology 2007; 68: 312-313. Fins JJ, Schiff ND, Foley KM. Late recovery from the minimally conscious state: ethical and policy implications. Neurology 2007; 68 304-307. Giacino JT, Hirsch J. Schiff N. Laureys S. Functional neuroimaging applications for assessment and rehabilitation planning in patients with disorders of consciousness. Arch Phys Med Rehabil2006; 87: S67-S76 Laureys S, Giacino JT, Schiff ND, Schabus M, Owen AM. How should functional imaging of patients with disorders of consciousness contribute to their clinical rehabilitation needs? Curr Opin Neurol 2006; 19: 520-527. Giacino JT. Kalmar K. Diagnostic and prognostic guidelines for the vegetative and minimally conscious states. Neuropsychol Rehabil 2005; 15: 166-174. Bosch-Bayard J, Valdes-Sosa P, Virues-Alba T, et al. 3D statistical parametric mapping of EEG source spectra by means of variable resolution electromagnetic tomography (VARE- TA). Clin Electroencephalogr 2001; 32: 47-61. Machado C, Cuspineda E, Valdes P, et al. Assessing acute middle cerebral artery ischemic stroke by quantitative electric tomography. Clin EEG Neurosci 2004; 35: 116-124.

Prichep LS, John ER. Tom ML. Localization of deep white matter lymphoma using VARETA: a case study. Clin Electro- encephalogr 2001; 32: 62-66 Johnston B, Seshia SS Prediction of outcome in non-trau- matic coma in childhood. Acta Neurol Scand 1984, 69' 41 7-427.

special imaging facilities, whereas QEEGt data, like those used in this study, can be obtained at the bedside with con- ventional instrurnentation.10

Hence, the main result of this paper is that our 8-year- old PVS patient showed a broad activation of the EEG power spectrum when his mother talked to him, meanwhile no significant differences were found when unknown women spoke to him.

These results demonstrate recognition of the mother's voice and indicate high-level residual linguistic processing in a patient meeting clinical criteria for VS. These findings launch new ethical and practical implications for the man- agement of VS patients.

13. John ER, Prichep LS, Kox W, et al. Invariant reversible QEEG effects of anesthetics. Conscious Cogn 2001; 10: 165-183.

14. Worsely KJ, Taylor JE, Tomaiuolo F, Lerch J. Unified univari- ate and multivariate random field theory. Neuroimage 2004;

15. Purhonen M, Kilpelainen-Lees R, Valkonen-Korhonen M, Karhu J, Lehtonen J. Cerebral processing of mother's voice compared to unfamiliar voice in 4-month-old infants. Int J

16. Maddock RJ, Garrett AS, Buonocore MH. Posterior cingulate cortex activation by emotional words: fMRI evidence from a valence decision task. Hum Brain Mapp 2003; 18: 30-41

17. Korein J. Ontogenesis of the fetal nervous system: the onset of brain life. Transplant Proc 1990; 22: 982-983.

18. Korein J. Reality and the brain: the beginnings and endings of the human being. Brochman J, (ed). The Reality Club. New York: lynx Books; 1988: 71-105.

19. DeCasper AJ, Spence MJ. Prenatal maternal speech influ- ences newborn perception of speech sounds. Infant Behav Develop 1986, 9: 133-150.

20. DeCasper AJ, Maugais R, lecanuet JP, Granier-Deferre C, Busnel MC. Familiar and unfamiliar speech elicit different cardiac responses in human fetuses. Presented lntl SOC Develop Psychol. Annapolis, MD; 1986.

21 DeCasper AJ. Fifer WP. Of human bonding newborns prefer their mothers' voices. Science 1980; 208: 1174-1176.

22. Di HB, Yu SM, Weng XC, et al. Cerebral response to patient's own name in the vegetative and minimally conscious states. Neurology 2007; 68: 895-899.

23 Owen AM, Menon DK, Johnsrude IS, et al. Detecting residual cognitive function in persistent vegetative state. Neurocase

24. Owen AM, Coleman MR, Boly M. Davis MH, Laureys S, Pickard JD. Detecting awareness in the vegetative state. Science 2006; 313: 1402.

23 (SUPPI 1): S189-SI95.

PsychOphysiol2004; 52: 257-266.

2002; 8: 394-403.


clin eeg neurosci 2007 machado 124 6

Documents