Neurophysiologie clinique 33 (2003) 23–30
www.elsevier.com/locate/neucli

Original article

Event-related brain potentials in a patient with akinetic mutism
Potentiels cérébraux cognitifs au cours du mutisme akinétique.
À propos d’un cas
Boris Kotchoubey a,*, Manfred Schneck b, Simone Lang a, Niels Birbaumer a,c
a

Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Gartenstr. 29, 72074 Tübingen, Germany
b
Section of Neurorehabilitation, Münster Clinics, Zwiefalten, Germany
c
Center for Cognitive Neuroscience, University of Trento, Italy
Received 12 June 2002; accepted 26 November 2002

Abstract
The clinical pattern of complete akinetic mutism (AM) was observed in a patient with a bilateral infarction of the anterior cerebral arteries
extending to the rostral cingulate cortex and the supplementary motor areas. Since the patient was unable to produce any overt response,
event-related brain potentials (ERPs) were used to obtain information about cortical processing of stimuli. Oddball tasks with simple
acoustical stimuli and semantic categories were used. Verbal processing was further assessed by comparing event-related potentials to words
compatible versus incompatible to the semantic context. Although the pattern of cortical responses was abnormal, differential responses were
clearly obtained to semantically different word classes. Thus, the hypothesis about cortical non-responsivity of AM patients, drawn from
several previous reports, was not supported. An ERP examination in AM patients can deliver information about their mental state, provided that
the stimuli and tasks possess a wide range of informational complexity and motivational value.
© 2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved.
Résumé
Le tableau clinique du mutisme akinétique (MA) complet a été observé chez un patient présentant un infarctus bilatéral des artères
cérébrales antérieures se prolongeant au cortex cingulaire antérieur et aux aires motrices supplémentaires. Puisque le patient ne pouvait pas
produire une réponse manifeste, les potentiels cérébraux liés aux événements (ERP) ont été utilisés comme moyen d’obtenir des informations
sur le traitement cortical des stimuli. Nous avons employé des tâches « oddball » en utilisant des stimuli acoustiques simples et des catégories
sémantiques. Le traitement verbal a été encore évalué en comparant les potentiels cérébraux liés aux événements selon que les mots sont
compatibles ou incompatibles par rapport au contexte sémantique. Bien que le tableau des réponses corticales fût anormal, des réponses
différentielles furent obtenues en réponse à des catégories sémantiques différentes ; en conséquence, l’hypothèse que le cortex des patients
avec MA ne réagit pas aux informations de l’environnement, tirée de plusieurs rapports précédents, n’a pas été confirmée. L’étude des ERP
chez des patients peut fournir des informations sur leur état mental, à condition que les stimuli et les tâches possèdent un haut degré de
complexité informationnelle et de valeur motivationnelle.
© 2003 Éditions scientifiques et médicales Elsevier SAS. Tous droits réservés.
Keywords: Akinetic mutism; Cognitive processes; Event-related potentials
Mots clés : Les potentiels liés aux événements ; Mutisme akinétique ; Processus cognitifs

* Corresponding author.
E-mail address: boris.kotchoubey@uni-tuebingen.de (B. Kotchoubey).

© 2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved.
DOI: 1 0 . 1 0 1 6 / S 0 9 8 7 - 7 0 5 3 ( 0 3 ) 0 0 0 0 3 - 0

24

B. Kotchoubey et al. / Neurophysiologie clinique 33 (2003) 23–30

Akinetic mutism (AM) is a rare syndrome characterized
by (i) complete or almost complete immobility (akinesia)
without paralysis and (ii) a lack of verbal contact. Most
frequently, AM results from a bilateral damage of the anterior
cingulate gyri and the supplementary motor area (SMA),
which is usually caused by a stroke in the domain of the
arteria cerebri anterior [1,34]. The clinical pattern of AM has
also been described following lesions of the thalamus (e.g.,
[17,36]), globus pallidus (e.g., [31,51]), and mesencephalic
brain stem structures (e.g., [6,14,37,38]).
There is a considerable controversy concerning the homogeneity of the AM syndrome. On the one hand, there seem to
be clinical differences between the fronto-thalamic and the
mesencephalic form [47], and some authors suggest that only
the former is the “true” AM [1], while patients with more
caudal lesions represent a variety of the so-called apallic
syndrome or “vegetative state”. On the other hand, there
appear to be common pathophysiological mechanisms of
all forms of AM [19,38], the most probable candidate
being injury to corticostriatopallidal–thalamocortical loops
[31,46].
The homogeneity of the AM syndrome is rarely warranted. Nemeth et al. [38] reported several AM patients
whose state fluctuated from coma through AM to the
locked-in syndrome. In some cases, AM was caused by
toxical lesions and infections of the central nervous system
[22,24,51], whose diffuse effects may substantially differ
from those of the relatively circumscribed vascular lesions.
Very little, if anything, is known about cognitive functions in
AM. In typical cases, the lack of overt responses makes the
use of standard neuropsychological tests impossible. The
sensory and association cortices are, as a rule, spared in these
patients. Thalamic lesions, which can lead to sensory disorders, constitute a minority of the reported cases. Accordingly,
early cortical evoked potentials are normal, suggesting that
the primary analysis of sensory signals is intact [22]. Some
consider AM as a primary disorder of motivational or drive
functions with relatively intact cognition (e.g., [1,19]). In
fact, the term “mutism” presupposes the lack of expressive
speech but intact language comprehension.
In contrast, other authors regard this condition as a form of
severe cognitive impairment close to a vegetative state [37].
The view of AM as the complete loss of consciousness was
presented in a well-known and authoritative book of Damasio [15]. This view is consistent with a well-replicated finding that EEG rhythmic activity in AM patients does not
respond to stimulation [6,22,36,37]. Thus, even though sensory signals do successfully arrive at the cortex, nothing is
known about their further processing there. Given that the
measured EEG responses to simple visual stimuli are mainly
mediated by the intact occipital cortex, it remains unclear as
to what may constitute the basis of this non-responsivity.
It appears reasonable to employ a more precise technique
for the assessment of cortical functions in AM. This is the
technique of event-related brain potentials (ERPs), which
allows a highly differentiated evaluation of different aspects

of information processing in the cortex. In healthy subjects,
this method is used for study of cognitive processing independent of the overt response [13,32]. In clinical neurology,
ERPs were used to reveal cognitive functions in several
conditions in which patients are unable to perform motor
responses, such as coma [18], vegetative state [27], and the
locked-in syndrome [40].
On the basis of the (more traditional) view reflected in the
term AM, one might expect that ERP waves related to perceptual processes, memory updating, semantic analysis, etc.
would be close to normal, with possibly decreased amplitudes over the region of the lesion. The opposite account,
which places AM in the vicinity of vegetative state and coma,
would lead to the other prediction, i.e., that brain waves
reflecting cortical information processing would be lacking
or, at least, would not vary as a function of stimulus features.
Given that the most simple and usual ERP paradigms have
been shown to heavily involve the damaged anterior cingulate (e.g., [11,49]), the former (i.e., most optimistic) prediction does not seem very probable. However, any option
between the two extremes cannot be ruled out a priori.
1. Materials and methods
1.1. Patient
S.V., female, 44 years old, right-handed, never seriously
ill before, was hospitalized due to a sudden series of seizures
with disoriented consciousness. Neurological and angiographic examination revealed a subarachnoidal hemorrhage
from an aneurysm of the ramus communicans anterior with
severe brain swelling. Later on, the same day, the patient
became completely non-responsive and had to be artificially
ventilated. The liquor pressure remained uncontrollable despite massive anti-edema therapy, and on day 52 after disease
onset, a ventriculoperitoneal shunt was installed. After this
operation, her state improved substantially: her reactions to
pain and other simple stimuli as well as her ability to track
moving objects with the gaze stabilized. Her sleep–wakefulness cycle also normalized. Then, the tracheostoma was
removed.
CT (an example on day 95 is presented in Fig. 1) showed
large hypodense areas in both frontal lobes in the basin of the
anterior cerebral arteries, which extended over the motor
cortex up to the Rolandic fissure. Necrotic areas were also
found in the right temporal lobe. The lateral and the third
ventricles, and the fourth ventricle to a lesser degree, were
enlarged. No considerable changes were found in subsequent
CT examinations.
On day 90 (the day of the first ERP recording), the patient
appeared to be oriented in the environment, with vivid reflexes. Her gaze followed moving objects, she was able to
swallow but was not able to chew. No verbal contact was
possible and no motor response on request was produced.
Slight spastic tetraparesis was more pronounced in the legs
than in the arms. An EEG demonstrated a general slowing of

B. Kotchoubey et al. / Neurophysiologie clinique 33 (2003) 23–30

25

Fig. 1. CT of patient S.V. shows a nearly complete destruction of the brain tissue in the domain of the anterior cerebral arteries on both sides. A further lesion
in the right temporal lobe can be seen.

rhythmic activity with fronto-central delta-waves. A comparison between rest and stimulation conditions did not reveal any difference in the EEG power spectrum.
Two months later, on the day of the second ERP recording,
there was an alleviation of the tetraparesis with reduced
spasticity as compared with the previously described state.
S.V. was able to wipe off the saliva at her mouth using a towel
placed in her hand. More complex movement patterns, such
as giving a hand in response to somebody else’s hand, or
playing back a thrown ball, appeared from time to time, but
were inconsistent. During ERP recording, the patient actively responded with head and eye movements to every
change in the environment, watching cables and connections
of devices. As compared with the previous measurement, the
EEG revealed a substantial increase of alpha (8–13 s–1)
activity and decrease of theta and delta oscillations. Stimulation led to a decrease of alpha and an increase of faster EEG
activity, as compared with rest.
1.2. Procedure
The ERP examinations were approved by the ethical committee of the University of Tübingen. Two measurements
were conducted during which the patient was sitting in a
wheelchair. Due to the unreliable eye fixation, only acoustic
(binaural) stimuli were used. The following stimulation paradigms were used:
(i) Habituation. Ten trains each of which entailed ten
1000-Hz 50-ms tones were presented with 2 s pauses
between the trains. Interstimulus intervals (ISIs, i.e.,
the intervals between the onset of two consecutive
stimuli) within a train were 300 ms. ERPs in this

condition were averaged, first, over each train (indicating the between-train habituation), and second, across
all first, all second, ..., all 10th stimuli (indicating the
within-train habituation).
(ii) Oddball. This condition consisted of the presentation
of two sine tones (800 and 1300 Hz) with ISIs of
850 ms. The former tone had a probability of occurrence of 15% and served as a rare target, i.e., the
patient was told to count it, although we were unable,
due to the lack of behavioral responses, to control
whether this instruction was followed. The other
stimulus had a probability of 85% (standard). A total
of 300 tones was administered (i.e., 45 targets and 255
standards). In controls, this paradigm results in a parietal positive ERP component P3 (e.g., [44]).
(iii) Semantic oddball [26]. In this condition, animal
names were used as a target stimulus category, and
other frequent nouns (jobs, body parts, household
objects, and plants) served as standards. A total of 75
words was used (15 words in each semantic category), each of which was presented four times. The
order of presentation was randomized, except that the
same word was never presented twice in a row. The
patient was instructed to count animal names ignoring
all other words. ISIs were 1 s.
(iv) Word pair [23]. Fifty pairs of strongly associated
one-syllable very frequent words (e.g., day–night)
and 50 pairs of unrelated words (e.g., man–table)
were presented in a random order. The associative
strength for each word pair had previously been assessed by a group of healthy subjects. ISIs were
500 ms, and interpair intervals were 1.2 s.

26

B. Kotchoubey et al. / Neurophysiologie clinique 33 (2003) 23–30

(v) Sentences [28]. Fifty simple sentences with an expected end word (e.g., we live on the planet earth)
were interspersed with 50 similar sentences with an
incongruent end word (e.g., the waiter brought ice
cream with earth). ISIs between words varied from
300 to 600 ms and the intervals between sentences
were 2 s.

1.3. Data acquisition and analysis
The EEG was recorded using Ag/AgCl electrodes placed
at F3, Fz, F4, C3, Cz, C4, P3, Pz, and P4 leads according to
the international 10–20 system, referred to the two mastoid
electrodes linked via a 10-kΩ shunt. The low-pass filter was
set at 70 Hz (with a further digital filtering at 30 Hz), and the
time constant was 0.3 s. The vertical and horizontal EOG
were recorded by means of electrodes attached above and
below the right eye, and at the outer canthi of the eyes,
respectively. The signal was digitized with the rate of 250 s–1.
Trials containing EEG amplitudes >100 µV were discarded.
Eye movement artifacts were corrected using regression
technique. ERPs were averaged off-line over an epoch of
1100 ms (400 ms in the habituation condition), including a
100-ms pre-stimulus baseline.
Two methods were used to assess the reliability of S.V.’s
ERP responses. In the univariate approach, the mean area
under the ERP curve was measured in each single trial within
a selected time window corresponding to the sought wave.
These data were analyzed by means of an analysis of variance with factors condition (e.g., frequent versus rare stimuli
in oddball tasks; appropriate versus inappropriate words in
the sentence task) and topography (i.e., electrode sites). In
the multivariate approach, all data points between 300 and
812 ms were presented as two vectors (according to the two
conditions characterizing a given task), which were wavelettransformed (in order to reduce the number of interrelated
variables) and compared by means of the Hotelling T2-test
[27]. The two techniques have different advantages and disadvantages. The univariate method is prone to test only those
waves which are similar to those obtained in healthy subjects,
ignoring possible latency differences. On the other hand, the
multivariate method takes into consideration too many irrelevant variables, which do not contribute to the difference
between conditions and thus diminish the test power. It
should be noted, however, that in most cases, the two approaches led to the same result indicating that this result was
not produced by the particular features of each statistical
technique. Moreover, these two analyses were also applied to
the data recorded in the two EOG channels in order to control
the condition that a significant ERP difference did not result
from any eye movement artifact that might have remained
uncorrected. In no task, significant differences were found in
the EOG channels.

Fig. 2. ERPs of S.V. in oddball conditions (top and middle panels). Thick
line: rare targets; thin line: frequent standards. For simplicity, only four
electrode sites are presented in this and the following figure. A distinct
cortical response P1–N1–P2 at Cz can be seen. At C4, late positive waves
differentiate between tagets and standards, this differentiation being highly
significant on the 1st but not on the 2nd examination. The vertical indicates
the similar shape and the identical peak latency (390 ms) of the target C4
waveform in both examinations. For comparison, the average response of six
healthy subjects in shown in the bottom panel. The longer latency of the late
positivity in S.V. than kn controls is a non-specific finding which occurs in
various neurological and psychiatric diseases [3,25]. More surprising is the
lack of this positivity at Pz, where it is the largest in healthy subjects.
Negativity in Figs. 2 and 3 is plotted upwards.

B. Kotchoubey et al. / Neurophysiologie clinique 33 (2003) 23–30

27

2. Results
2.1. Primary cortical responses
During the first examination, all non-verbal stimuli elicited a distinct primary complex of cortical waves N1–P2 with
latencies of around 120 and 210 ms, respectively (Fig. 2).
This complex habituated both between trials and between
trains. When averaged across the first versus the last trials in
all the trains, the peak-to-peak N1–P2 amplitude decreased
from 16 to 8 µV. In the comparison between the first and the
last train, the corresponding figures were 19 and 9 µV. During
the second examination, the N1–P2 complex was also clearly
expressed in response to verbal stimuli, suggesting better
synchronization of neural generators responsible for cortical
auditory responses. Both between-trial and between-train
habituation effects were obtained.
2.2. Oddball
The late P3-like wave distinguishing between targets and
standards had an atypical scalp distribution reaching a maximum amplitude of about 8 µV at the right fronto-central
locations (Fig. 2). In the first examination, this positivity to
rare stimuli in the interval 300–500 ms was highly significant
(univariate P < 0.005; multivariate P < 0.001). Although a
very similar positive wave was recorded in the second examination as well (Fig. 2), it did not reach significance
(P > 0.20). Earlier ERP components such as P1, N1 and P2,
did not discriminate between targets and standards.
2.3. Semantic tasks
In the semantic oddball paradigm, which required understanding the experimenter’s instruction and the ability for
semantic classification, a late positive wave quite similar to
that in the non-verbal oddball was obtained (Fig. 3). Importantly, this wave measured over the 500–700 ms interval was
significant on both first (univariate P < 0.05; multivariate
P < 0.02) and second examinations (univariate P < 0.05;
multivariate P < 0.05). No differential response was found in
the word pairs and sentences paradigms.

3. Discussion
Although AM is often discussed under the general rubric
“disorders of consciousness” [2,10,21,47,48], there are no
empirical data as to what is happening in the minds of those
patients and how far the higher cortical functions underlying
their consciousness are disturbed. The typical general impression from AM patients, precisely depicted as “appearance of vigilance” (see [46], p. 1214; [47], p. 441) cannot
substitute objective data, notwithstanding possible methodological difficulties discussed in the following paragraphs.
The present study is the first one in which the sensitive
technique of event-related potentials was employed to obtain

Fig. 3. ERPs in the semantic oddball task during the first (top panel) and
second examinations (middle panel). The average ERPs of six healthy
subjects are presented in the bottom panel for comparison. For the legend,
see Fig. 2.

the data of whether the abilities to differentiate between the
stimuli according to their physical and semantic qualities are
still preserved in an AM patient.
3.1. Patient
The low incidence of AM makes it virtually impossible to
conduct studies with a homogenous and statistically sound

28

B. Kotchoubey et al. / Neurophysiologie clinique 33 (2003) 23–30

patient sample. The maximum information about this syndrome, therefore, is and will be obtained from single-case
studies. This should not, however, be said in an apologizing
tone, taking into consideration that single-case observations
have built a firm basis of modern neuropsychology [7,8]. S.V.
possessed many “classical” AM features: large bilateral lesion of the medial frontal cortex involving the cingulate
cortex and the SMA, without damage of the brain stem
structures responsible for vigilance; complete loss of voluntary motor activity and active communication; EEG slowing
with fronto-central delta-waves. Her gaze followed moving
objects and persons in her environment but she was unable to
perform any instruction. At the second examination, behavioral and physiological (a-rhythm) data indicated the beginning of recovery. On the other hand, the patient became more
distractable. Other features were rather atypical, such as the
large lesion in the right temporal lobe and mild pyramidal
signs, which, however, cannot explain her total immobility.
To summarize, although AM clearly prevailed in S.V.’s condition, we cannot rule out that some portion of her abnormalities should be attributed to additional lesions, not directly
related to the AM syndrome.
3.2. Reliability
Given the relatively small number of valid trials, a question of the reliability of the present ERP data may be posed.
For instance, some of the observed waves might be regarded
as non-averaged delta oscillations rather than the true
stimulus-evoked activity. These oscillations might eventually
have led to a statistically significant result simply by chance.
However, this supposition is at odds, first, with the similarity
of most data obtained in the two examinations, and second,
with the identity of the results obtained with univariate and
multivariate tests. The interpretation of positive and negative
findings should be distinguished. As regards the former (i.e.,
clear differences between conditions), the stability of the
S.V.’s N1–P2 wave complex and its habituation with stimulus repetition suggests that the primary signal analysis in the
auditory cortex and the most elementary learning processes
were preserved. The oddball paradigm with simple tones
yielded two very similar positivities having exactly the same
latency (both peaking at about 390 ms, see Fig. 2). Although
in the second examination the difference did not reach the
conventional significance level, this exact temporal coincidence seems unlikely to have appeared due to a random
overlap of stimulus-unrelated EEG-waves. In the semantic
oddball, both examinations led to statistically significant
results. The first time, the late positive wave discriminating
between standards and targets might eventually be attributed
to a shift of the whole target waveform (Fig. 3); however, that
shift was not significant while the late positivity to targets
was. In the second examination, there was no such shift at all,
yet the positive component was significant again. Given the
abnormal morphology and topography (see below), we do
not assert that the obtained ERP components are indeed those
described in general psychophysiology as P300 or P600.

What can be said is that there were differentiated cortical
responses to semantically different word classes, which indicates that at least some cortical mechanisms underlying language comprehension were preserved.
The low signal–noise ratio usually decreases the probability of obtaining a reliable ERP difference. This fact underscores the value of the above-mentioned consistent positive
findings, but it also stresses the caution required for the
interpretation of negative findings. For instance, the P300
wave is often abnormal in many patients with much milder
morphological and behavioral changes than those observed
in S.V. (for review, see [3,25]). Moreover, each of the expected ERP phenomena can occasionally be lacking in a
completely healthy individual as well (e.g., [44]). These
factors cannot, however, explain the clearly abnormal scalp
distribution of oddball responses, as well as the fact that both
semantic mismatch paradigms led to zero results in both
examinations.
In sum, the present data show that the idea of cortical
non-reactivity in AM [15,37,38] was obviously based on the
insufficient sensitivity of the recording of EEG rhythmic
responses. An AM patient can be able to process stimulus
information at different levels of complexity. On the other
hand, our data also do not provide support for the more
traditional view, namely that AM is mainly a disorder of
motivation and action control [1,19] consisting of the interruption of the pathway between the “central executive” and
the motor system. Such a view implies that the information
processing would be intact up to the point where a decision
about the response is made. This was not the case in S.V.
Although the present data do not allow us to describe the
exact nature of her cognitive deficit, there is no doubt that
some kind of cognitive impairment was present, which cannot be explained by purely motivational factors.
3.3. Damaged brain areas and cognitive dysfunctions
Two brain structures were completely destroyed by the
stroke in S.V.: the SMA and the anterior cingulate gyrus
(ACG). Both are critically involved in the organization of
voluntary movements [16,45,50]. However, some data indicate the activity of SMA and pre-SMA during tasks which do
not require overt responding, such as time perception [29] or
memory recall [5]. The main function of the ACG is presently
conceived of as the monitoring of conflicts between incompatible responses (see [4,12,20,30]). On the other hand, evidence is being accumulated that the dorsal part of the ACG
may exert attentional control of stimulus processing, even
independent of motor action [9,11,35], although it remains
unclear as to whether the same ACG region is involved in
both perception- and action-related attentional control
[33,39], or whether these processes are topographically distributed within the anterior cingulate [41].
It should be noted that relatively circumscribed ACG lesions (e.g., cingulotomy to cure intractable pain, see [42] for
review) never result in massive cognitive deficits comparable
with AM. Similar to S.V., most AM patients have much larger

B. Kotchoubey et al. / Neurophysiologie clinique 33 (2003) 23–30

lesions, which exceed SMA and ACG. These lesions have
been suggested to affect the so-called gating systems [47]
through which the frontal cortex exerts its control over the
thalamic mechanisms of attentional tuning of sensory signals
[52]. Interestingly, despite the enormous importance of these
structures in warranting normal cognitive functioning, they
may not be directly involved in the maintenance of vigilance,
since patients in a permanent vegetative state may possess a
high degree of intactness of these circuits [46]. It may be
speculated that, whereas the disruption of these corticostriatopallidal–thalamocortical loops leads to the clinical pattern
of AM, the preserved function of these loops may underlie
fragmented cortical processing in vegetative patients [43]. In
line with this idea is the fact that the most clear positive result
in S.V. was obtained in the semantic oddball demanding
active following of the experimental instruction, whereas the
two semantic mismatch tasks in which passive listening is
required yielded no response; exactly the opposite is typical
for patients in a vegetative state and minimal consciousness
state [27]. This pattern may be explained by the inability to
sustain attention spontaneously, but it also indicates the importance of such factors as the salience or motivational value
of stimuli.

Acknowledgements
This study was supported by the German Research Society (DFG). The technical assistance of V. Bostanov and M.
Riess is appreciated.

References
[1]

Ackermann H, Ziegler W. Akinetischer mutismus—eine Literaturübersicht. Fortschr Neurol Psychiat 1995;63:59–67.
[2] Assal G. Les syndromes deficitaires post-traumatiques. Arch Suiss
Neurol Neurochir Psychiat 1985;4:17–24.
[3] Barrett G. Clinical application of event-related potentials in dementing illness: issues and problems. Int J Psychophysiol 2000;37:49–53.
[4] Botvinick M, Nystrom LE, Fissel K, Carter CS, Cohen JD. Conflict
monitoring versus selection-for-action in anterior cingulate cortex.
Nature 1999;402:179–81.
[5] Buckner RL, Raichle ME, Miezin FM, Petersen SE. Functional anatomic studies of memory retrieval for auditory words and visual
patterns. J Neurosci 1996;16:6219–35.
[6] Cairns HWB. Disturbances of consciousness with lesions of brainstem and diencephalon. Brain 1952;75:109–45.
[7] Caramazza A. On drawing inferences about the structure of normal
cognitive systems from the analysis of patterns of impaired
performance: the case for single-patient studies. Brain Cogn 1986;5:
41–66.
[8] Caramazza A, Badecker W. Clinical syndromes are not god’s gift to
cognitive neuropsychology: a reply to a rebuttal to an answer to a
response to the case against syndrome-based research. Brain Cogn
1991;16:211–27.
[9] Carlsson K, Petrovic P, Skare S, Petersson KM, Ingvar M. Tickling
expectations: neural processing in anticipation of a sensory stimulus. J
Cogn Neurosci 2000;12:691–703.
[10] Celesia GG. Persistent vegetative state. Theor Med 1997;18:221–36.

29

[11] Clark VP, Fannon S, Lai S, Benson R, Bauer L. Responses to rare
visual target and distractor stimuli using event-related fMRI. J Neurosci 2000;83:3133–9.
[12] Cohen JD, Botwinick M, Carter CS. Anterior cingulate and prefrontal
cortex: who’s in control? Nature Neurosci 2000;5:421–3.
[13] Coles MGH, Gratton G, Fabiani M. Event-related potentials. In:
Caccioppo JT, Tassinari LG, Petty RE, editors. Tutorials in
Psychophysiology: Physical, Social, and Inferential Elements. Cambridge, UK: University Press; 1990. p. 413–55.
[14] Daly DD, Love JG. Akinetic mutism. Neurology 1958;8:236–42.
[15] Damasio AR. The Feeling of What Happens: Body and Emotion in the
Making of Consciousness. San Diego: Harcourt; 1999.
[16] Deecke L, Grözinger B, Kornhuber HH. Voluntary finger movement
in man: cerebral potentials and theory. Biol Cybern 1976;23:99–119.
[17] Domburg PH, ten Donkelaar HJ, Notermans LH. Akinetic mutism
with bithalamic infarction: neurophysiological correlates. J Neurol
Sci 1996;139:58–65.
[18] Fischer C, Morlet D, Bouchet P, Luaute J, Jourdan C, Salord F.
Mismatch negativity and late auditory evoked potentials in comatose
patients. Clin Neurophysiol 1999;110:1601–10.
[19] Fisher CM. Honored guest presentation: Abulia minor vs. agitated
behavior. Clin Neurosurg 1983;31:9–31.
[20] Gehring WJ, Knight RT. Prefrontal-cingulate interactions in action
monitoring. Nature Neurosci 2000;3:516–20.
[21] Giacino JT. Disorders of consciousness: differential diagnosis and
neuropathologic features. Semin Neurol 1997;17:105–11.
[22] Gutling E, Landis T, Kleihues P. Akinetic mutism in bilateral necrotizing leucoencephalopathy after radiation and chemotherapy: electrophysiological and autopsy findings. J Neurol 1992;239:125–8.
[23] Hagoort P, Brown CM, Swaab TY. Lexical-semantic event-related
potential effects in patients with left hemisphere lesions and aphasia
and patients with right hemisphere lesions without aphasia. Brain
1996;119:627–49.
[24] Hayashi R, Hanyu N, Kuwabara T, Moriyama S. Serial computed
tomographic and electroencephalographic studies in Creutzfeldt–Jakob disease. Acta Neurol Scand 1992;85:161–5.
[25] Kotchoubey B. Do event-related brain potentials manifest mental
(cognitive) processes? J Psychophysiol 2002;16:129–49.
[26] Kotchoubey B, Lang S. Event-related potentials in a semantic auditory oddball task in humans. Neurosci Lett 2001;310:93–6.
[27] Kotchoubey B, Lang S, Bostanov V, Birbaumer N. Is there a mind?
Psychophysiology of unconscious patients. News Physiol Sci 2002;
17:38–42.
[28] Kutas M, Hillyard SA. Reading senseless sentences: brain potentials
reflect semantic incongruity. Science 1980;207:203–5.
[29] Lacruz F, Artrieda J, Pastor MA, Obeso JA. The anatomical basis of
somaesthetic temporal discrimination in humans. J Neurol Neurosurg
Psychiat 1991;54:1077–81.
[30] MacDonald AW, Cohen JD, Strenger VA, Carter CS. Dissociating the
role of the dorsolateral prefrontal and anterior cingulate cortex in
cognitive control. Science 2000;288:1835–8.
[31] Mega MS, Cohenour RC. Akinetic mutism: disconnection of frontalsubcortical circuits. Neuropsychiat Neuropsychol Behav Neurol
1997;10:254–9.
[32] Meyer DE, Osman AM, Irwin DE, Yantis S. Modern mental chronometry. Biol Psychol 1988;26:3–67.
[33] Miltner WHR, Braun C, Coles MGH. Event-related brain potentials
following incorrect feedback in a time-estimation task: evidence for a
“generic” neural system for error detection. J Cogn Neurosci 1997;9:
788–98.
[34] Minagar A, David NJ. Bilateral infarction in the territory of the
anterior cerebral arteries. Neurology 1999;54:886–8.
[35] Nakamura N, Yamamoto T, Saito T, Fujita H. Analysis of activation in
anterior cingulate cortex during cognitive process of selection following somatosensory stimuli: fMRI study with elaborate task paradigms. Magnet Res Imag 2000;18:397–404.

30

B. Kotchoubey et al. / Neurophysiologie clinique 33 (2003) 23–30

[36] Nemeth G. Some theoretical and practical aspects of the disturbances
of consciousness with special reference to akinetic mutism. Funct.
Neurol 1988;3:9–28.
[37] Nemeth G, Hegedüs K, Molnar L. Akinetic mutism and locked-in
syndrome: the functional-anatomical basis for their differentiation.
Funct. Neurol 1986;1:128–39.
[38] Nemeth G, Hegedüs K, Molnar L. Akinetic mutism associated with
bicingular lesions: clinicopathlgical and functional anatomical correlates. Eur Arch Psychiat Neurol Sci 1986;237:218–22.
[39] Niki H, Watanabe M. Prefrontal and cingulate unit activity during
timing behavior in the monkey. Brain Res 1979;171:213–24.
[40] Onofrj M, Thomas A, Paci C, Scesi M, Tombari R. Event related
potentials recorded in patients with locked-in syndrome. J Neurol
Neurosurg Psychiat 1997;63:759–64.
[41] Peterson BS, Skudlarski P, Gatenby JC, Zhang H, Anderson AW,
Gore JC. An fMRI study of Stroop word–color interference. Biol
Psychiat 1999;45:1237–58.
[42] Peyron R, Laurent B, Garcia-Larrea L. Functional imaging of brain
responses to pain. A review and meta-analysis. Neurophysiol Clin
2000;30:263–88.
[43] Plum F, Schiff ND, Ribary U, Llinas R. Coordinated expression in
chronically unconscious persons. Philos Trans Roy Soc London 1998;
353:1929–33.
[44] Polich J, Kok A. Cognitive and biological determinants of P300: an
integrative review. Biol Psychol 1995;41:103–46.

[45] Sakamoto A, Lüders H, Burgess R. Intracranial recordings of
movement-related potentials to voluntary saccades. J Clin Neurophysiol 1991;8:223–33.
[46] Schiff ND, Ribary U, Moreno DR, Beattie B, Kronberg E, Blasberg R,
Giacino J, McCagg C, Fins JJ, Llinas R, Plum F. Residual cerebral
activity and behavioral fragments can remain in the persistently vegetative brain. Brain 2000;125:1210–34.
[47] Schiff ND, Plum F. The role of arousal and “gating” systems in the
neurology of impaired consciousness. J Clin Neurophysiol 2000;17:
438–52.
[48] Spittler JF. Krankheitsbedingte Bewußtseinsstörungen: Grundlagen
ethischer Bewertungen. Fortschr Neurol Psychiat 1999;67:37–47.
[49] Stevens AA, Skudlarski P, Gatenby JC, Gore JC. Event-related fMRI
of auditory and visual oddball tasks. Magnet Res Imag 2000;18:
495–502.
[50] Uhl F, Kornhuber AW, Wartberger P, Lindinger G, Lang W, Deecke L.
Supplementary motor area in spatial coordination of bilateral
movements: a new aspect to ’the SMA debate’. EEG Clin Neurophysiol 1996;101:469–77.
[51] Ure J, Faccio E, Videla H, Caccuri R, Giudice F, Ollari J, et al.
Akinetic mutism: a report of three cases. Acta Neurol Scand 1998;98:
439–44.
[52] Yingling CD, Skinner JE. Gating of thalamic input to the cerebral
cortex by nucleus reticularis thalami. In: Desmedt JE, editor. Attention, Voluntary Contraction, and Slow Potential Shifts. Basel: Karger;
1977. p. 70–96.