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Classical conditioning in the vegetative and minimally conscious state

Abstract

Pavlovian trace conditioning depends on the temporal gap between the conditioned and unconditioned stimuli. It requires, in mammals, functional medial temporal lobe structures and, in humans, explicit knowledge of the temporal contingency. It is therefore considered to be a plausible objective test to assess awareness without relying on explicit reports. We found that individuals with disorders of consciousness (DOCs), despite being unable to report awareness explicitly, were able to learn this procedure. Learning was specific and showed an anticipatory electromyographic response to the aversive conditioning stimulus, which was substantially stronger than to the control stimulus and was augmented as the aversive stimulus approached. The amount of learning correlated with the degree of cortical atrophy and was a good indicator of recovery. None of these effects were observed in control subjects under the effect of anesthesia (propofol). Our results suggest that individuals with DOCs might have partially preserved conscious processing, which cannot be mediated by explicit reports and is not detected by behavioral assessment.

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Figure 1: Stimulus design and different stages of the EMG response.
Figure 2: Learning during the anticipatory interval.
Figure 3: Single-subject measures of learning during the anticipatory interval.
Figure 4: Learning, clinical measures and prediction of recovery.
Figure 5: Nonassociative learning in patients and control subjects: changes in the response to the aversive stimulus.
Figure 6: Intact latencies, but smaller amplitudes, in event-related auditory potentials in DOCs.

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Acknowledgements

We thank the care homes and rehabilitation centers in the UK and Argentina, the Cambridge Impaired Consciousness Research Group, the staff of the Wellcome Trust Research Facility for their contribution, and all the study's participants. We especially thank F. Klein and the Anesthesia Favaloro Team. We also thank L. Naccache and C. Koch for comments on an early version of the manuscript. This study was funded by an Antorchas Foundation grant (T.A.B.), a Marie Curie IIF grant (T.A.B.), a StartUp grant (F.F.M.), the Human Frontiers Science Program (M.S.) and a Medical Research Council Acute Brain Injury Collaborative grant (G0600986).

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Authors and Affiliations

Authors

Contributions

T.A.B. and C.F. designed the study. T.A.B. and F.F.M. conducted the behavioral and neurological assessments. T.A.B., C.F., M.R.C., M.H. and D.E.S. conducted the eye-blink conditioning task in the normal volunteers group and T.A.B., M.R.C. and C.F. conducted the task in the patient group. T.A.B., D.E.S., C.F., M.H., M.R.C., F.F.M. and M.S. analyzed and interpreted the data. T.A.B., D.E.S. and M.S. performed the statistical analysis. T.A.B., D.E.S. and M.S. drafted the manuscript. All of the authors revised the manuscript for important intellectual content.

Corresponding author

Correspondence to Tristan A Bekinschtein.

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Supplementary Figures 1–3 and Supplementary Tables 1–4 (PDF 1092 kb)

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Bekinschtein, T., Shalom, D., Forcato, C. et al. Classical conditioning in the vegetative and minimally conscious state. Nat Neurosci 12, 1343–1349 (2009). https://doi.org/10.1038/nn.2391

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