Communication in locked-in syndrome: Effects of imagery on salivary pH
DOI: 10.1212/01.wnl.0000228226.86382.5f
ISSN: 0028-3878
Accession: 00006114-200608080-00045

Wilhelm, B; Jordan, M; Birbaumer, N PhD

Volume 67(3), 8 August 2006, pp 534-535
Publication Type:
[Clinical/Scientific Notes]
©2006AAN Enterprises, Inc.
From the Institute of Medical Psychology and Behavioral Neurobiology (B.W., M.J., N.B.), University of Tübingen, Germany; and Human Cortical Physiology Unit (N.B.), NIH, Bethesda, MD.
Additional material related to this article can be found on the Neurology Web site. Go to and scroll down the Table of Contents for the August 8 issue to find the title link for this article.
Editorial, see page 380
Supported by the Deutsche Forschungsgemeinschaft (DFG; Bi 195) and NIH (HD30146/EB00856).
Disclosure: The authors report no conflicts of interest.
Received April 11, 2005. Accepted in final form March 28, 2006.
Address correspondence and reprint requests to Dr. N. Birbaumer, Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Gartenstrasse 29, D-72074 Tübingen, Germany; e-mail: Tel: +49-07071-2974219; Fax: +49-07071-29-5956

Patients with completely locked-in syndrome are conscious and alert, even though they have lost the ability to control their muscles.1 These patients require a communication channel independent of the motor system. EEG-based brain–computer interfaces (BCIs) are an available communication aid, but aside from the intensive training that most of them demand, not all patients achieve proficiency in EEG control. Here we report an alternative method to re-establish communication in a 46-year-old woman with ALS. At the time of the study, she had been diagnosed with ALS for more than 5 years and had been artificially ventilated and fed for 3 years. For 12 months before this study, she was completely locked in, showing no signs of voluntary motor control including eye movements (measured with electro-oculogram) and external sphincter activity (measured with an anal electromyography electrode). Before entering the locked-in state, the patient requested continuation of life support from her family. The family insisted on respecting the patient's will beyond the locked-in state. EEG responses derived from auditory event–related paradigms indicated preserved cognitive functions,2 which, together with the experiment described below, excludes persistent vegetative state. Prior to this experiment, the patient participated in BCI training as described elsewhere,3 which was terminated after 6 months without success. Because of this failure, we hypothesized that subdural electrode placement and recording, which offer greater signal-to-noise-ratio than scalp EEG recordings, would provide a greater chance of BCI communication. After consultation with the ethics committee and the patient's husband, we elected to pursue this. To reinstate communication and to obtain informed consent, we tested a new means of communication based on manipulation of the salivary pH. Salivary flow can be elicited by imagery of food.4,5 As flow rate increases upon stimulation, the concentration of bicarbonate increases, resulting in an increase in salivary pH.6

First, we determined whether the patient was capable of manipulating the salivary pH by food imagery. Three sessions with 10 trials each were performed. Each trial consisted of a 2-minute rest period to establish a baseline and a response period lasting 2 minutes. The pH was measured by a digital pH meter (GPRT-1400-AN; Greisinger Electronic GmbH, Germany). The pH electrode was placed in the oral cavity. After each trial, the saliva was removed from the patient's mouth. During the test period, the patient was required to imagine the taste of either lemon or milk. A nonrandomized order (five trials of lemon imagery followed by five trials of milk imagery, and vice versa) was chosen to determine consistent pH responses upon repeated imagery of the same stimulus. There was a difference between pH of nonstimulated baseline saliva and pH of stimulated saliva for both imagery conditions (p < 0.001); mean pH increased during lemon imagery and decreased during milk imagery (figure, A, task A). Next, the feasibility of the pH response for communication was tested by means of questions with known answers. Three sessions were performed as described above. The patient was asked to respond to questions (e.g., “My name is …” [for a sampling of questions, see appendix E-1 on the Neurology Web site at ]), 12 times per session. The questions were phrased as yes- and no-answer questions, half with “yes” or “true” answer and half with “no” or “false,” presented in random order. The patient was instructed to use imagery of lemon/milk for answering yes/no. Increase/decrease of pH (pH value after 2 minutes of food imagery minus pH value after 2 minutes of rest) with a minimum change of ±0.01 was taken as a valid yes/no answer. In this manner, 32 (89%) of 36 questions were answered correctly and 4 (11%) incorrectly (figure, B, task B). Finally, the patient confirmed the decision for subdural implantation of EEG electrodes using pH communication: During three sessions, the patient was asked to give informed consent to implantation (“Do you agree to …?” or “You do not agree to …?”), 12 times per session in one 60-minute session. Each stimulus (lemon or milk) was associated with agreement on 50% of the trials and disagreement on 50%. Increase/decrease of the pH with a minimum change of ±0.02 was taken as a valid answer. The patient agreed 27 times (100%) out of a total of 27 valid answers (figure, B, task C). The implantation was realized without any complications and resulted in clean and high-amplitude electrocorticographic recordings as predicted. Attempts for BCI communication, however, were not successful until now.

Figure. Salivary pH changes and accuracy during tasks. (A) Imagery of lemon (n = 15), imagery of milk (n = 15). (B) Respond to questions with “yes” with lemon imagery (n = 18) and with “no” with milk imagery (n = 18). (C) Give informed consent, agreement with lemon imagery (n = 9)/with milk imagery (n = 9), and disagreement with lemon imagery (n = 9)/with milk imagery (n = 9). (Top) Box-and-whisker plots representing the median and mean value, with 50% of all data falling within the box. The “whiskers” extend to the 5th and 95th percentiles. ***p < 0.001. (Bottom) Percentage of correct pH responses (accuracy). (A, B) Imagery of lemon/yes-answer questions: increase of pH >=0.01, and imagery of milk/no-answer questions: decrease of pH >=0.01. (C) Agreement with lemon imagery/disagreement with milk imagery: increase of pH >=0.02, and agreement with milk imagery/disagreement with lemon imagery: decrease of pH >=0.02.

The results of this experiment demonstrate that a completely locked-in patient is capable of manipulating salivary pH by food imagery. The pH response has proven to be reliable and precise enough to allow the patient to communicate with her environment. Although pH communication cannot compete with BCI-based communication in speed, it is an alternative. It has proven to be easy to apply with a minimum of technical and financial effort and can be used without intensive training. To generalize these findings, further investigations in a larger sample of patients are required.


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