Skip to Article Content

Skip to Article Information

Wiley Online Library

Search within
Search term

Login / Register
Psychophysiology
Psychophysiology
Free Access
Breaking the silence: Brain–computer interfaces (BCI) for communication and motor
control
Niels Birbaumer
First published: 25 September 2006
https://doi.org/10.1111/j.1469-8986.2006.00456.x
Citations: 440
Address reprint requests to: Niels Birbaumer, Ph.D., Institute of Medical
Psychology and Behavioral Neurobiology, MEG-Center, University of Tübingen,
Gartenstrasse 29, D-72074 Tübingen, Germany. E-mail: niels.birbaumer@uni-
Tuebingen.de.

The author and his work are supported by the Deutsche Forschungsgemeinschaft (DFG)
and the National Institutes of Health (NIH). The editor, Bob Simons, made
invaluable suggestions and corrections at all stages of the manuscript's
preparation. The comments of two anonymous reviewers, of Many Donchin, Andrea
Kübler, Theresa Vaughan, and Jon Wolpaw are greatly appreciated. The data from my
laboratory presented here could not have been realized without a functioning
interdisciplinary research team: the names of the team members appear in the
references cited. They deserve all the credit for this work. The manuscript was
prepared during my stay as a research fellow at the NIH, NINDS, Bethesda, MD: My
friend Leonardo Cohen, M.D., Chief of the Human Cortical Physiology Section at
NINDS, and Cornelia Weber made the time in Washington, DC, a unique and productive
experience.
Sections
PDFPDF
Tools
Share
Abstract

Brain–computer interfaces (BCI) allow control of computers or external devices with

regulation of brain activity alone. Invasive BCIs, almost exclusively investigated
in animal models using implanted electrodes in brain tissue, and noninvasive BCIs
using electrophysiological recordings in humans are described. Clinical
applications were reserved with few exceptions for the noninvasive approach:
communication with the completely paralyzed and locked-in syndrome with slow
cortical potentials, sensorimotor rhythm and P300, and restoration of movement and
cortical reorganization in high spinal cord lesions and chronic stroke. It was
demonstrated that noninvasive EEG-based BCIs allow brain-derived communication in
paralyzed and locked-in patients but not in completely locked-in patients. At
present no firm conclusion about the clinical utility of BCI for the control of
voluntary movement can be made. Invasive multielectrode BCIs in otherwise healthy
animals allowed execution of reaching, grasping, and force variations based on
spike patterns and extracellular field potentials. The newly developed fMRI-BCIs
and NIRS-BCIs, like EEG BCIs, offer promise for the learned regulation of emotional
disorders and also disorders of young children.
A brain–computer interface (BCI) or brain–machine interface (BMI) activates
electronic or mechanical devices with brain activity alone. BCIs and BMIs allow
direct brain communication in completely paralyzed patients and restoration of
movement in paralyzed limbs through the transmission of brain signals to the
muscles or to external prosthetic devices. We differentiate invasive from
noninvasive BCIs: Invasive BCIs use activity recorded by brain implanted micro- or
macroelectrodes, whereas noninvasive BCIs use brain signals recorded with sensors
outside the body boundaries.

The brain signals employed for invasive BCIs to date include (1) action potentials
from nerve cells or nerve fibers (Kennedy & Adams, 2003; Kennedy, Bakay, Moore,
Adams, & Goldwaithe, 2000), (2) synaptic and extracellular field potentials
(Nicolelis, 2001; Serruya, Hatsopoulos, Paninski, Fellows, & Donoghue, 2002), and
(3) electrocorticograms (ECoG; Lal et al., 2005; Leuthardt, Schalk, Wolpaw,
Ojemann, & Moran, 2004). The noninvasive BCIs used (1) slow cortical potentials
(SCP) of the EEG (Birbaumer et al., 1999), (2) EEG and MEG oscillations, mainly
sensorimotor rhythm (SMR), also called mu-rhythm (Pfurtscheller, Neuper, &
Birbaumer, 2005; Pfurtscheller, Neuper, et al., 2003; Wolpaw, Birbaumer, McFarland,
Pfurtscheller, & Vaughan, 2002), (3) P300 and other event-related brain potentials
(ERPs; Farwell & Donchin, 1988), (4) BOLD response in functional magnetic resonance
imaging (fMRI; Hinterberger et al., 2004; Weiskopf et al., 2003; Weiskopf,
Scharnowski, et al., 2005), and (5) near-infrared spectroscopy (NIRS) measuring
cortical blood flow (Coyle, Ward, Markham, McDarby, 2004; Sitaram et al., in
press).

This article reviews the research concerned with invasive and noninvasive BCIs from
the perspective of their clinical usefulness for communication and motor
restauration in paralysis. The reviews available on invasive BCI in animals
(Nicolelis, 2003; Nicolelis, Birbaumer & Mueller, 2004; Schwartz, Taylor, &
Tillery, 2001) describe primarily the performance of single neuronal unit resonse
patterns for the reconstruction of movement sequences in healthy animals; if they
discuss clinical applications in human patients at all, a science fiction
perspective of what may be possible is given without reference to the few published
clinical applications. The noninvasive BCI literature overviews (Kübler,
Kotchoubey, Kaiser, Wolpaw, & Birbaumer, 2001; Wolpaw et al., 2002) were based on
small numbers of clinical cases; meanwhile the database for BCI research in
clinical populations has broadened and allows some tentative theoretical and
clinical conclusions not available in previous reviews. Remarkably, the clinical
applications, particular those of BCIs for communication in completely paralyzed
patients, allow a fresh view on some old and still unresolved theoretical questions
in psychophysiology:

What is the role of voluntary motor control and of the feedback following motor
responses in goal directed thinking and imagery and verbal behavior?
2

What are the consequences of a loss of complete or virtually complete loss of

motor behavior on emotional responding at the subjective and the physiological
level?
3

What is the nature and extent of brain reorganization after complete cessation
of voluntary motor response systems? What are the consequences of compensatory
brain reorganization on behavior?

This review addresses these questions in the context of BCI research and tries to
illustrate once again the usefulness of a union between clinical and experimental
approaches in psychophysiology for the reformulation of some basic scientific
problems in the field.
History of BCI Research

Hans Berger, who discovered the human EEG, speculated in his first comprehensive
review of his experiments with the “Elektrenkephalogramm” (1929) about the
possibility of reading thoughts from the EEG traces by using sophisticated
mathematical analyses. Grey Walter, the brilliant EEG pioneer who described the
contingent negative variation (CNV), often called the “expectancy wave,” built the
first automatic frequency analyzer and the computer of “average transients” with
the intention of discriminating covert thoughts and language in the human EEG
(Walter, 1964). Fetz (1969) published the first paper on invasive operant
conditioning of cortical spike trains in animals. Only the recent development of
BCIs, however, has brought us a bit closer to the dreams of these pioneers of EEG
research.

Invasive and noninvasive BCIs originate from different research traditions, though
both have their roots in animal experiments. Invasive BCIs consist of implanted
multielectrode grids in the motor cortex of paralyzed patients (Donoghue, 2002),
premotor cortex of monkeys (Carmena et al., 2003), or parietal motor command areas
(Schwartz et al., 2001). They try to reconstruct intended skilled movements from
neuronal firing patterns online. Based on “sparse coding” approaches to motor
learning (Riehle & Vaadia, 2005) and directional coding vectors of motor neurons
(Georgopoulos, Schwartz, & Kettner, 1986), automatized complex movements can be
reconstructed online from relatively few motor neurons using simple algorithms:
Nicolelis' group (Carmena et al., 2003) demonstrated in monkeys after extensive
training of a reaching and grasping movement that firing patterns of 32 neurons are
sufficient to execute that movement directly with an artificial limb. Chapin,
Moxon, Markowitz, and Nicolelis (1999) trained rats to move a lever with an
artificial arm in a Skinner box for reward with extracellular firing of cortical
cells without any actual movement. The neuronal firing pattern that used to precede
and accompany the lever pressing response alone was able to operate on the lever
delivering the reward.
Operant Conditioning of Autonomic Functions

The second root of BCI research is intimately tied to the tradition of biofeedback
and instrumental-operant learning of autonomic functions. During the late 1960s and
early 1970s, Neal E. Miller and collaborators opposed the traditional wisdom of the
autonomous nervous system (ANS) as autonomous and independent of voluntary control
of the somatic central nervous system (CNS). Miller (1969), in a landmark paper in
Science, challenged that view that voluntary control is acquired through operant
(instrumental) conditioning whereas modification of involuntary ANS functions is
learned through classical (Pavlovian) conditioning, a distinction first emphasized
by Skinner (1953; Holland & Skinner, 1961).

Miller presented experimental evidence in curarized and artificially ventilated

rats showing that even after long-term curarization of several weeks, the animals
learned to increase and decrease heart rate, renal blood flow, and dilation and
constriction of peripheral arteries in an operant conditioning paradigm rewarding
the animals for increases and decreases of these specific physiological functions.
These studies stirred an enormous interest in the scientific and clinical
community, particularly in psychosomatic medicine and behavior modification.

The results suggested that instrumental (“voluntary”) control of autonomic

functions is possible without any mediation of the somatic-muscular system. Operant
training of any internal body function seemed possible, opening the door for
psychological and learning treatment of many medical diseases such as high blood
pressure, cardiac arrhythmias, vascular pathologies, renal failure,
gastrointestinal disorders, and many others. In the clinic, biofeedback of these
functions replaced the operant conditioning in rats, the feedback from the specific
physiological variable constituted the reward (for an overview of these years'
enthusiasm, see the Aldine series on Biofeedback and Self-Control; Kamiya, 1971).

During the next two decades, Miller and his students at Rockefeller University
tried to replicate their own findings. Figure 1 shows the steady decline of the
size of the conditioning effect with each replication. Finally, by the mid-1980s,
it was impossible to replicate the previous effects. Barry Dworkin, Neal Miller's
last and most prolific student, continued to try and build the most sophisticated
“intensive care unit” for curarized rats, but again, operant training of autonomic
function or nerves in the curarized rat was impossible.
Details are in the caption following the image
Figure 1
Open in figure viewer
PowerPoint

Effects of operant learning of heart rate control in the curarized rat rewarded
with intracranial rewarding brain stimulation (triangles) and shock avoidance
(circles). Replications of the same experiment from 1966 to 1970 (from Dworkin &
Miller, 1986).

In contrast, classical conditioning succeeded even in single facial nerve fibers

(Dworkin, 1993; Dworkin & Miller, 1986). Dworkin attributed the failure of operant
techniques to the missing homeostatic effect of the reward: The reward acquires its
positive effect through homeostasis-restoring effects (i.e., ingestion of food
restores glucostatic and fluid balance). In the curarized rat (and the completely
paralyzed respirated and fed patient?), where all body functions are kept
artificially constant, the homeostatic function of the reward is no longer present
because imbalances of the equilibrium do not occur.

The chronically curarized rat and the completely paralyzed, artificially ventilated
and fed locked-in patient share many similarities; difficulties in communicating
with these patients may be understood based on these similarities.

The difficulties in replicating the operant learning of autonomic variables were

accompanied by an “awakening” in the clinical arena of biofeedback applications:
The most impressive clinical results were achieved with electromyographic feedback
in chronic neuromuscular pain (Flor & Birbaumer, 1993), neuromuscular
rehabilitation of various neurological conditions (Birbaumer & Kimmel, 1979),
particularly external spincter control in enuresis end encopresis (Hölzl &
Whitehead, 1983), and posture control in kyphosis and scoliosis (Birbaumer, Flor,
Cevey, Dworkin, & Miller, 1994; Dworkin et al., 1985), but there were clinically
unimpressive or negligible results in essential hypertension (Engel, 1981; McGrady,
Olson, & Kroon, 1995), heart rate (Cuthbert, Kristeller, Simons, Hodes, & Lang,
1981), and gastric hyperfunction (Hölzl & Whitehead, 1983). It became painfully
clear that only very limited positive effects of biofeedback on visceral pathology
with clinically and statistically relevant changes occur. There was one notable
exception, however: neurofeedback of brain activity (Elbert, Rockstroh,
Lutzenberger, & Birbaumer, 1984).
Seizure Control

The most spectacular and popularized results in the emerging field of biofeedback
(or “physiological regulation” as it is presently called) were the self-regulation
of brain waves (Kamiya, 1971). Increase and decrease of alpha frequency of the EEG
were supposed to create “meditative” states with many beneficial effects in the
periphery and on behavior. Theta wave augmentation and reduction had profound
effects on vigilance and attention (Birbaumer, 1977). Slow cortical potentials
(SCP) control allowed anatomically specific voluntary regulation of different brain
areas with area specific effects on behavior and cognition (for an overview, see
Rockstroh, Elbert, Birbaumer, & Lutzenberger, 1989). Warning voices such as
experiments by Mulholland and his group (Mullholland & Evans, 1966) demonstrating
perfect control of alpha waves through manipulation of the oculomotor system and
decoupling of eye fixation went largely unheard.

Sterman (Sterman, 1981; Sterman & Friar, 1972) was the first to propose self-
control of epileptic seizures (Elbert et al., 1984) by an augmentation of
sensorimotor rhythm (SMR). SMR in human subjects is recorded exclusively over
sensorimotor areas with frequencies of 10 to 20 Hz and variable amplitudes.
Pfurtscheller and colleagues (2005) localized the source of human SMR in the
sensorimotor regions following the homuncular organization of the motor and
somatosensory cortical strip. Imagery of hand movement abolishes SMR over the hand
region; imagery or actual movement of the legs blocks SMR in the interhemispheric
sulcus. Pfurtscheller called this phenomenon event-related desynchronization and
synchronization (Pfurtscheller et al., 2005).

On the basis of careful animal experiments (Sterman and Clemente, 1962a, 1962b),
Sterman demonstrated incompatibility of seizures in motor and premotor areas in the
presence of SMR. Cats exhibited maximum SMR during motor inhibition and various
sleep stages. Presence of spindles during different sleep stages, particularly
during rapid eye movement (REM) sleep indicated recruitment of inhibitory thalamo-
cortical circuits and blocked experimentally induced seizures. Sleep spindles and
SMR share identical physiological mechanisms. Epileptic cats and humans were
trained to increase SMR, and, after extensive training ranging from 20 to more than
100 sessions, Sterman (1977) was able to demonstrate seizure reduction and complete
remission in some patients with drug-resistant epilepsy. It is important to note
that SMR is often called mu-rhythm following a suggestion of Gastaut (Gastaut,
1952; Gastaut, Terzian, & Gastaut, 1952) who noted its abolition in some types of
seizures. However, it is not clear whether the neurophysiological bases of the two
phenomena are really comparable and therefore I recommend that the term SMR as used
by Sterman et al. be retained because of its well-defined theoretical and
experimental background.

It is not accidental that SMR operant control is achieved through activation and
deactivation of the central motor loops. Again, successful voluntary regulation of
a physiological variable is tied to the regulation of the motor system. The results
of SMR control in animals and patients seem to demonstrate that manipulation
(mediation) of the peripheral motor efferents is not a necessary requirement of SMR
control, at least on the basis of EMG recordings of the arm muscles showing no
measurable variation during motor imagery with central nervous system event-related
desynchronization (Pfurtscheller et al., 2005). The successful brain regulation of
SMR in completely paralyzed patients reported below confirms that changes of the
peripheral motor system do not mediate CNS activity responsible for SMR origin. The
notion of the critical role of CNS activity in voluntary action and thought
remains.

Beginning in 1979, our laboratory published an extensive series of experiments that

demonstrated operant control of slow cortical potentials in the EEG. These
demonstrations differed from previous brain biofeedback work as they documented the
following in well-controlled experimental paradigms:

Strong and anatomically specific effects of self-induced cortical changes on

behavior and cognition;
2

Solid neurophysiological evidence about anatomical sources and physiological

function of slow cortical potentials (for reviews, see Birbaumer, 1999; Birbaumer,
Elbert, Canavan, & Rockstroh, 1990; Birbaumer, Flor, Lutzenberger, & Elbert, 1995;
Birbaumer, Roberts, Lutzenberger, Rockstroh, & Elbert, 1992).

Of particular interest in the context of CNS motor mediation of voluntary control

of brain activity was the fact that SCPs originating from posterior parietal
sources were resistant to operant learning whereas central and frontal SCPs could
be brought under voluntary, operant control after one to five training sessions
(Lutzenberger, Roberts, & Birbaumer, 1993). Several clinical studies confirmed the
critical importance of the anterior brain systems for physiological regulation of
CNS functions: Lutzenberger et al. (1980) showed that patients with extended
prefrontal lobe lesions were unable to learn SCP control despite intact
intellectual functioning. Disorders with prefrontal dysfunctions such as attention
deficit disorder (ADD; Birbaumer, Elbert, Rockstroh, & Lutzenberger, 1986) and
schizophrenia (Schneider et al., 1992) exhibited extreme difficulties in acquiring
SCP control, and attentional improvement after SCP or SMR neurofeedback training
required long training periods (Strehl, Leins, Goth, Klinger, & Birbaumer, in
press). Again, peripheral motor function played no role in SCP conditioning
(Birbaumer & Kimmel, 1979), but intact prefrontal systems seemed to be a
prerequisite for successful brain control. Figure 2 shows the results of a study
where healthy subjects learned SCP control, and fMRI (BOLD response) was recorded
simultaneously during training.
Details are in the caption following the image
Figure 2
Open in figure viewer
PowerPoint

Effects of self-regulation of slow cortical potentials (SCP) on regional metabolic

changes measured with fMRI. Left: BOLD responses during self-produced cortical
negativity (left column) and positivity (right column). Red colored brain areas
indicate activation, green color deactivation. Right: A: Activation of anterior
basal ganglia during self-induced cortical positivity. B: Related deactivation of
premotor areas during cortical positivity (from Hinterberger, Veit, et al., 2005)

Subjects received visual feedback of positive and negative SCPs of 6 s duration and
were rewarded for the production of target amplitudes (Hinterberger et al., 2004;
Hinterberger, Birbaumer, & Flor, 2005; Hinterberger, Veit, et al., 2005). As
illustrated in Figure 2, successful voluntary brain control depends on activity in
premotor areas and the anterior parts of the basal ganglia. Birbaumer et al. (1990)
had proposed earlier that physiological regulation of SCP and attention depends
critically on anterior basal ganglia activity regulating local cortical activation
thresholds and SCP in selective attention and motor preparation. Braitenberg
(Braitenberg & Schüz, 1991) created the term “thought pump” (“Gedankenpumpe” in
German) for this basal ganglia–thalamus–cortical loop. Taken together, the
extensive literature on the SCP also suggests that operant-voluntary control of
local cortical excitation thresholds underlying goal-directed thinking and
preparation depends on an intact motor or/and premotor cortical and subcortical
system.

Encouraged by the reliable and lasting effects of brain self-regulation on various

behavioral variables and by Sterman's case demonstrations, Birbaumer and colleagues
conducted several controlled clinical studies on the effect of SCP regulation on
intractable epilepsy (Kotchoubey et al., 2001; Rockstroh et al., 1989, 1993). Based
on their neurophysiological model of SCP regulation, patients with focal epileptic
seizures were trained to down-regulate cortical excitation by rewarding them for
cortical positive potentials and perception of SCP changes. After extremely long
training periods, some of these patients gained close to 100% control of their SCPs
and seizure suppression, tempting Birbaumer and colleagues to apply cortical
regulation as a BCI for paralyzed patients: Given that epileptic patients suffering
from a dysregulation of cortical excitation and inhibition and consequent brain
lesions learn to control their brain responses both within the laboratory and in
daily life, it is not unreasonable to ask whether a paralyzed patient could learn
to activate an external device or computer in order to move a prosthetic arm or to
convey messages to a voice system.
Noninvasive BCIs for Communication in Paralysis

Amyotrophic Lateral Sclerosis (ALS) is a progressive motor disease of unknown

etiology resulting in a complete destruction of the peripheral and central motor
system but only affecting sensory or cognitive functions to a minor degree (Norris,
1992). There is no treatment available; patients have to decide to accept
artificial respiration and feeding after the disease destroys respiratory and
bulbar functions for the rest of their life or to die of respiratory problems. If
they opt for life and accept artificial respiration, the disease progresses until
the patient loses control of the last muscular response, which is usually the eye
muscle or the external sphincter. The resulting condition is called completely
locked-in state (CLIS). If rudimentary control of at least one muscle is present,
we speak of a locked-in state (LIS). Other conditions leading to a locked-in state
are subcortical stroke and other extended brain lesions, Guillain-Barre syndrome,
some rare cases of Parkinson disease, and Multiple Sclerosis.

Based on the extensive knowledge and clinical experience acquired with SCP control,
Birbaumer et al. (1999) developed a BCI system for ALS patients. As in the epilepsy
studies, patients were first trained to produce positive or negative SCPs upon the
command of an auditory cue. They watched their SCP changes or, in case of
insufficient vision, received auditory feedback and reward for target amplitude
changes (Kübler, Kotchoubey, et al., 2001; Kübler, Neumann, et al., 2001). After
achieving more than 70% control, letters or words are presented on a computer
screen or spoken by a word program. Patients select a letter by successively
reducing letter strings containing the desired letter by creating SCPs after
appearance of the desired letter (Birbaumer et al., 1999; Birbaumer, Hinterberger,
Kübler, & Neumann, 2003; Kübler, Kotchoubey, et al., 2001; Perelmouter & Birbaumer,
2000; Tregoubov & Birbaumer, 2005; Wolpaw et al., 2002). Thirty-two patients with
ALS at various stages of their disease were trained to use the SCP-BCI. Eventually,
seven of these patients arrived at the locked-in state and were able to continue to
use the BCI. Seven additional patients began training after entering the complete
locked-in state; none of them achieved lasting BCI control and communication. One
of these CLIS patients communicated shortly with a pH-based communication system
but lost this control after two sessions (Hinterberger, Birbaumer, et al., 2005;
Wilhelm, Jordan, & Birbaumer, 2006).

The SCP-BCI needs long training periods, sometimes months, in the home of the
patient (all patients were artificially respirated and paralyzed), and letter
selection speed is slow, usually one minute per letter. However, speed is not an
issue in artificially respirated paralyzed patients devoting all their cognitive
and emotional energies to communication (Birbaumer, Strehl, & Hinterberger, 2004).
The SCP-BCI needs professional attention and continuous technical support; easy
application by family members or nonprofessional caretakers was possible in only
one patient.

Wolpaw and colleagues at the Wadsworth Laboratories at Albany, New York, did an
extensive series of experiments mainly with healthy persons using SMR rather than
SCP as the target brain response (Wolpaw et al., 2002). In a group of patients, two
with high spinal cord lesions, Wolpaw and McFarland (2004) demonstrated that
multidimensional control of a cursor movement on a computer screen can be learned
in just a few sessions of training: The subjects were able to move a cursor within
10 s into one of eight goals appearing randomly at one of the four corners of the
screen. The flexibility, speed, and learning performance is generally equal to that
seen when invasive multielectrode BMI systems are tested in animals. The Wolpaw and
McFarland (2004) preparation consisted of a simple electrode montage covering the
hand and foot area with a linear online filtering and detection algorithm used for
data reduction and quantification. Most subjects employed right and left hand and
feet imagery to reach the target goals in SMR-BCI.

The Albany and Tübingen group joined forces in an NIH-funded project and compared
the feasibility and performance of the SCP-BCI, the SMR-BCI, and the P300-BCI
developed by Farwell and Donchin (1988) in seven pre-LIS ALS patients in a balanced
within-subject design. The results were clear-cut: All patients achieved sufficient
performance rates (more than 70% of the trials correct) after 20 sessions with SMR-
BCI training, four of the seven could spell with the P300-BCI, but none of the
patients achieved acceptable performance rates with the SCP-BCI despite significant
differentiation between negative and positive SCP. It can be concluded that in ALS
patients with functioning vision and eye control, SMR-BCI and P300-BCI shows the
most promising results. The project continues to follow these patients into
complete paralysis and eventually into the complete locked-in state. Figure 3 gives
examples of the training situations for the three BCIs.
Details are in the caption following the image
Figure 3
Open in figure viewer
PowerPoint

Three types of BCIs. A: BCI using slow cortical potentials (SCP depicted at the
top). Patient selects one letter from the letter string on screen (right below)
with positive SCPs, the spelled letters appear on top of the screen. B: SMR-BCI.
Top right: SMR oscillations from sensorimotor cortex during inhibition of movement
and imagery or execution of movement (EEG trace below). On the left part of the
picture is the feedback display with the target goal on the right side of the
screen indicating the required SMR increase (target at bottom) or SMR decrease
(target at top). The curser reflecting the actual SMR is depicted in red moving
from the right side of the screen toward the target goal. C: P300-BCI. Rows and
columns of letter strings are lighted in rapid succession. Whenever the desired
letter (P) is among the lighted string, a P300 appears in the EEG (after Sellers &
Donchin 2006; Piccione et al. 2006).

SCP-BCIs need more extensive training than other BCI modes but may have the best
stability and independence of sensory, motor, and cognitive functioning necessary
for its application to the LIS and the CLIS patients. The patients described
earlier (Birbaumer et al., 1999) had high success rates with SCP-BCI training but
only after many more sessions.

Together with the introduction of controlled clinical trials to document

comparative BCI performance, the Albany–Tübingen group created a Web site, BCI 2000
(http://www.bciresearch.org/BCI2000/bci2000.html; Schalk, McFarland, Hinterberger,
Birbaumer, & Wolpaw, 2004) providing free software modules for BCI applications in
research and clinic. More than 100 laboratories are now regular contributors to the
BCI 2000 Web site, improving both the hardware and software modules. The aim is an
inexpensive, FDA and CE approved, easy-to-use, universal, noninvasive BCI that will
allow SCP, SMR, P300, and other possible oscillatory brain activities (i.e., gamma
band in ECoG) in a world wide net of participants whose data collection and
analysis will contribute to the continuous improvement and validity of BCI
applications.

Long training periods, noisy signals, the continuous professional attention

necessary, slow spelling speed, electrode and skin problems with long recording
times, and the controlled attention focus during spelling makes the invasive BCI
approach an attractive alternative, at least at a theoretical level.
Invasive BCIs for Communication

Kennedy, Kirby, Moore, King, and Mallory (2004) published several single cases with
ALS in different stages (none either LIS or CLIS), with a cortically implanted
glass microelectrode filled with a neurotrophic growth factor. The axon of the cell
targeted by the electrode grows into it and allows recording of the spike activity.
Some of the patients learned to spell using the spike activity mainly by turning it
on and off in a “yes” or “no” fashion. From the published material, it is difficult
to judge the usefulness of this preparation because death and medical complications
interrupted communication in several cases (one case reportedly used the device on
a more continuous basis). None of the patients were in urgent need of the device
because all had rudimentary motor control.

Brunner, Graimann, Huggins, Levine, and Pfurtscheller (2005), Graimann, Huggins,

Levine, and Pfurtscheller (2004), and Pfurtscheller, Mueller, Pfurtscheller,
Gerner, and Rupp (2003) implanted subdural electrodes in presurgical epileptic
patients and demonstrated that control of SMR synchronization and desynchronization
can be achieved in one to several sessions. Spelling was not required.

More than 100 scientists attending the 2005 BCI conference in Rennselearville, New
York, were asked for their opinion on the future of BCI applications. The majority
of the BCI researchers present at the conference believed that the noninvasive BCI
showed the most promise for development during the next decade. The main argument
against noninvasive BCIs was their limited capacity to represent more than two
signal alternatives (“yes,”“no,”“select,”“ignore,” etc.), and this limitation would
prohibit their use for motor restoration or motor neuroprosthesis applications
(Carmena et al., 2003; Taylor, Tillery, & Schwartz, 2002). This argument was
recently countered experimentally by Wolpaw and McFarland (2004), who demonstrated
two-dimensional cursor control over the sensorimotor rhythm of the scalp EEG. Even
high-level motor control of complex movements combined with sophisticated
prosthesis design can be exerted with a two-dimensional command system. In earlier
papers by Elbert et al. (summarized in Birbaumer et al., 1990), healthy
participants were trained to produce differential frontal, central, parietal, and
left-right hemispheric negative and positive slow cortical potential shifts,
allowing them at least several degrees of freedom for cursor or prosthesis control
(see Birbaumer at al., 1990, for a review).

A further argument against widespread use of noninvasive BCIs for motor control and
communication consists of the long training periods required and the high error
rates that are observed even after extensive training. Patients often need weeks to
learn to produce a particular brain response voluntarily in order to select letters
or words reliably above chance. Although healthy persons may achieve brain control
within one or two sessions, patients need a minimum of 20 sessions to achieve more
than 70% correct selections at least with sensorimotor rhythm or slow cortical
potentials (Kübler, Nijboer, et al., 2005). The incorporation of more sophisticated
algorithms for EEG classification did not improve the situation substantially
(Hinterberger, Kübler, Kaiser, Neumann, & Birbaumer, 2003; see results of the BCI
competition in the IEEE Transactions in Biomedical Engineering; Nicolelis et al.,
2004). Papers by Hinterberger, Veit, et al. (2003) and Piccione et al. (2006)
illustrate this point nicely; they report equivalent results for BCI control with
different classification algorithms (Hill et al., in press).

In humans, there are two published reports, in addition to the already mentioned
attempts by Pfurtscheller's group, on invasive BCIs with epileptic patients. In
these experiments, subdural macroelectrodes were implanted over frontal regions,
and patients attempted spelling or they performed imagery tasks (Lal et al., 2005;
Leuthardt et al., 2004). In a single session with these patients, it was possible
to differentiate imagination of hand, tongue, and mouth movement using the ECoG.
Figure 4 shows the perfect nonoverlapping classification of hand and tongue
movements at the sensorimotor cortex (Support Vector Machines, SVM, were used as
classification algorithms; see Lal et al., 2004; Schröder et al., in press),
allowing the patient to select letters at a speed of several letters per minute
after a 20-min training session. Patients spelled by selecting letters with imagery
of finger movement (green field at cortex in Figure 4) and rejecting a letter by
imagery of tongue movement (red field at cortex of Figure 4).
Details are in the caption following the image
Figure 4
Open in figure viewer
PowerPoint

Support-vector-machine (SVM) classification of electrocorticogram (ECoG) of a

presurgically implanted 64-electrode grid over frontal cortex. Patient imagined
finger movement to select a letter (indicated by the finger on the screen, lower
part of figure, left) and tongue movement to reject a letter (indicated by
Einstein's tongue, lower right). Upper part: classification result for all
frequencies from 7 to 100 Hz. Red shows the classification for tongue imagery,
green for finger projected on the cortical surface of the same patient.

This indicates, not surprisingly, that with subdurally implanted macroelectrodes,

degrees of freedom, precision of classification, and success rates may
substantially improve. The first implantation of 100 microelectrodes in the motor
cortex of a high spinal cord patient by Donoghue et al. (personal communication)
and Hochberg, Mukand, Polykoff, Friehs, and Donoghue (2005) seems to allow improved
BCI performance. However, of 17 ALS patients in our sample, all in the final stage
of the disease and all artificially respirated and fed, only 1 agreed to
implantation of subdural macroelectrodes (Wilhelm et al., 2006). Even when informed
about the possibilities and advantages of the surgical implantation, 16 patients
refused the procedure and preferred the slow and error-prone noninvasive device. An
important argument of patients was that time is not an issue if one is completely
paralyzed (Birbaumer et al., 1999, 2004; Kübler et al., 2003; Kübler, Nijboer, et
al., 2005).

It is fair to conclude, therefore, that noninvasive BCIs using different types of

EEG signals such as slow cortical potentials, P300, or SMR oscillations at present
are and will remain the method of choice for communication in paralyzed and
hopefully also in completely locked-in patients with ALS and other debilitating
neurological diseases (subcortical stroke, Guillain Barré, extensive brain damage).
If patients, their families, and the local ethical committees agree, implantations
of micro- or macroelectrodes subdurally or in brain tissue should be considered.
However, the database of invasive BCIs for communication purposes in paralyzed
patients at present is too small to judge their efficacy, and the willingness of
patients and their families to agree to implantation is weak as long as the
noninvasive BCIs are available and functioning. The slow spelling speed and high
error rate (even in highly trained patients rarely above 80% trials correct) of
noninvasive EEG-based BCIs is well tolerated by paralyzed patients with a different
life perspective and an urgent need to communicate.
Operant Learning, Thinking and BCI Control in the Complete Locked-in State

As mentioned above, none of the ALS patients starting BCI training after entering
the complete locked-in state acquired stabile communication (n=17). Again, one of
these patients was implanted with subdural electrodes over the left frontal cortex.
Despite clean ECoG recordings and extensive learning attempts over several weeks,
no communication was achieved.

The most frequent argument explaining the lack of communication in the complete
locked-in state assumes that with progression of ALS or Guillain-Barré Syndrome
deterioration of cognitive functions prevents learning and communication (see
Sellers & Donchin, 2006, for a discussion of the problem). It is difficult to
reject this argument empirically because neuropsychological testing for cognitive
functioning is impossible in a completely paralyzed person. We therefore developed
an ERP test with an extensive series of cognitive experimental paradigms ranging
from simple oddball-P300-evoking tasks to highly complex semantic mismatch N400 and
personalized memory tasks eliciting late cortical positivities (Hinterberger,
Birbaumer, et al., 2005; Kotchoubey et al., 2005).

More than 100 patients in responsive and nonresponsive vegetative state and 24 ALS
patients at different stages of the disease were tested. The relationships between
the complexity of a cognitive task and the presence or absence of a particular
component are rather inconsistent (Kotchoubey et al., 2005; Kotchoubey, Lang,
Bostanov, & Birbaumer 2002), meaning a patient may show absent early cortical
components such as N1 but normal P300, or absent P300 to simple tones but intact
P600 to highly complex verbal material. With one exception, all CLIS patients had
ERP responses to one or more of the complex cognitive tasks, indicating at least
partially intact processing stages in the complete locked-in state (Hinterberger et
al., 2005). Patients in the more advanced stages of ALS show slowing of waking EEG
sometimes into the theta band. This slowing may be, at least in part, caused by
episodes of anoxia due to inadequate functioning of artificial respiration. It is
often difficult to decide whether the patient is awake or in sleep stage 1 or 2.
One CLIS patient gave informed consent to implantation of electrodes in the brain
over a two-session period by answering “yes” with imagery of milk taste and “no” by
imagining lemon taste, and measurement of the pH level in mouth cavity mucosa
served as the dependent variable (Wilhelm et al., 2006). Responding with BCI and
the pH device was lost again after implantation in this patient. Slowing of the
ECoG and complete absence of gamma-band activity characterizes the recordings.

These ERP data neither prove nor disprove normal information processing in CLIS but
suggest some intact “processing modules” in most ALS patients with CLIS despite a
reduced general arousal. Three of the remaining 12 patients of our sample entered
LIS and continued to use the SCP-BCI for verbal communication, indicating transfer
of learning from rudimentary motor control (mostly eye movements) to LIS and
probably to CLIS also.

Assuming partially intact processing in ALS patients who are completely locked in
and possible transfer of already acquired BCI communication to CLIS, the question
of why the patients who entered the CLIS before learning BCI use did not acquire
control of their brain signals (SCP-BCI and SMR-BCI was tried on this CLIS group)
remains. Figure 1 demonstrating the failure to replicate operant (“voluntary”)
learning of visceral functions (see Dworkin & Miller, 1986) may provide an answer
to this question: Chronically curarized rats and people with longer time periods in
CLIS may lose the contingency between the required physiological behavior (SMR
decrease or heart rate increase) and its consequences (brain stimulation reward in
the curarized rat and letter selection in the patient). Extinction sets in due to
there being so few reinforced learning trials in the rat and in the completely
locked-in patient. No contingency remains at all: Thoughts and intentions are never
followed by their anticipated consequences in one's own behavior or in the behavior
of others, and thoughts and imagery and goal-directed feelings are extinguished.

Theories of consciousness come to a conclusion similar to learning theory accounts

of extinction of thinking. In a Hebbian tradition, associative binding between
distinct stages of neural activity was postulated as the crucial mechanism behind
conscious experience and perception of sensory and motor events (Singer & Gray,
1994/1995). The presence of localized gamma-band responses in the cortex functions
as an electrophysiological indicator of associative binding of cell assemblies into
meaningful percepts; its absence seems incompatible with conscious percepts and
“Gestalt” formation (Kaiser, Lutzenberger, Preissl, Ackermann, & Birbaumer, 2000).
Psychophysiological and psychophysical experiments comparing self-induced voluntary
actions with the same but involuntary movements caused by transcranial magnetic
stimulation (TMS) or external agents demonstrate that conscious decision and
perception of “will” depends on the close contiguity in time between the decision
and the response. Voluntary action and thoughts and their consequences are
attracted together in time; involuntary externally initiated and attributed
responses and their effects are experienced as more distant in time (Haggard,
Clark, & Kalogeras, 2002; Libet, Gleason, Wright, & Pearl, 1983). They are
consequently not interpreted as a conscious unit but separate cognitive elements
incapable of acquiring any contextual meaning. Virtually all thought–action–
consequence contingencies in a completely paralyzed person become externally
induced by patient-independent agents, usually the caretakers. The resulting
cognitive state and remaining information-processing capacities remain unclear
until the first CLIS patient communicates.

Under the assumption that passive-sensory information processing remains intact in

completely locked-in patients (see above), the failure to control autonomic
functions with operant learning in the curarized rat (see Dworkin & Miller, 1986)
and the described experiments on transcranial magnetic stimulation and voluntary
movement seem to provide converging evidence for the following: In the complete
locked-in state, the fact that intentional thoughts and imagery are rarely followed
by a rewarding or punishing stimulus (i.e., attention from others for that thought)
creates an extension of the subjective time perception of the interval between a
response (thought) and eventual consequences. Therefore, the probability for an
external event (e.g., attention of a family member) to function as a perception of
a causal contingency between the response (thought) and its consequence becomes
progressively smaller, and after a long CLIS it may vanish altogether. What fills
the subjective world may consist only of the few remaining external auditory and
tactile and visceral sensations bearing no contextual relationship between them.
With the lack of reinforcing contingencies controlling the maintenance of the
stream of thoughts, they extinguish slowly. As demonstrated by Haggard et al.
(2002), it is this lack of motor control consisting of intention (“will”),
preparation, execution, and sensory and external feedback that determines the
deteriorating subjective time estimation between response and its consequence.

Donchin (personal communication) assumes that “fooling” the system by providing

artificial stimulation such as TMS or electric brain stimulation contingent after a
particular neural respose may delay the extinction of goal-directed thinking. The
motor control factor responsible for the cessation of voluntary cognitive activity
and goal-directed thinking in the completely locked-in patient and the curarized
animal lends support to a “motor theory of thinking” similar to that discussed by
William James (1890).

Another consequence of response–consequence separation was described as “learned

helplessness” that characterized depression at the affective level and deficits in
problem solving at the cognitive level (Seligman, 1975). Surprisingly, the
commonsense prediction that complete paralysis accompanied by the loss of most
positive reinforcers should result in depression and despair was not confirmed. But
common sense and folk psychology often result in egregious errors.
Emotion and Quality of Life in ALS and Paralysis

Most ALS patients opt against artificial respiration and feeding and die of
respiratory problems. In many countries, doctors are allowed to assist the
transition with sedating medication to ease respiration-related symptoms. If
doctor-assisted suicide or euthanasia is legal, as it is in the Netherlands and
Belgium, very few patients vote for continuation of life. The vast majority of
family members and doctors (usually neurologists) believe that the quality of life
in total paralysis is extremely low and continuation of life constitutes a burden
for the patient and that it is unethical to use emergency measures such as
tracheostomy to continue life. The pressure on the patient to discontinue life is
enormous.

The facts on end-of-life issues and quality of life do not support hastened death
decisions in ALS, however, and the scientific literature and our own studies
challenge the pervasive myth of helplessness, depression, and poor quality of life
in respirated and fed paralyzed persons, particular with ALS (Albert, Rabkin, Del
Bene, Tider, & Mitsumoto, 2005; Quill, 2005). Most instruments measuring depression
and quality of life such as the widely used Beck or Hamilton depression scales are
invalid for paralyzed people living in protected environments because most of the
questions do not apply to the life of a paralyzed person (“I usually enjoy a good
meal,”“I like to see a beautiful sunset”). Special instruments had to be developed
for this population (Kübler, Winter, et al., 2005). In studies by Breitbart,
Rosenfeld, and Penin (2000) and by our group (Kübler, Winter, et al., 2005) only 9%
of the patients showed long episodes of depression, most of them in the time period
following the diagnosis and a period of weeks after tracheostomy. Figure 5 shows
the results for depression (A) and for quality of life (B) rated by patients and
family members and caretakers. As can be seen, ALS patients are not clinically
depressed. In fact, they are in a much better mood than psychiatrically depressed
patients without any life-threatening bodily disease. Likewise, patients rate their
quality of life as much better than their caretakers and family members do, even
when these patients are completely paralyzed and respirated. None of the patients
of our sample (some of them in LIS) requested hastened death.
Details are in the caption following the image
Figure 5
Open in figure viewer
PowerPoint

Depression and quality of life in ALS. A: Depression measured with a modified

version of the Beck Depression Inventory in healthy controls, ALS patients at
different stages of their disease, and psychiatrically depressed patients. ALS
patients are significantly more depressed than normals but within the normal range.
B: Quality of life in different dimensions of daily living for ALS patients (white
bars) and their significant others (green, usually family members). (From Kübler,
Nijboer, et al., 2005.)

It could be argued that questionnaires and interviews reflect more social

desirability and social pressure than the “real” behavioral–emotional state of the
patient. The social pressure in ALS, however, directs the patient toward death and
interruption of life support. The data, therefore, may underestimate the positive
attitude in these groups. This hypothesis is strongly supported by a series of
experiments with ALS patients at all stages of their disease using the
International Affective Picture System (IAPS; Lang, Bradley, & Cuthbert, 1999).
Lulé et al. (2005) and Lulé et al. (in press) using a selection of pictures with
social content, found more positive emotions to positive pictures and less negative
ratings to negative pictures in ALS than in matched healthy controls. Even more
surprising are the brain responses to the IAPS slides (Figure 6). FMRI measurement
in 13 patients with ALS and controls demonstrated increased activation in the
supramarginal gyrus and other areas responsible for empathic emotional responses to
others comparable to the “mirror neuron network” identified first by Rizolatti and
colleagues (Gallese, Keysers, & Rizzolatti, 2004). Furthermore, brain areas related
to the processing of negative emotional information such as the anterior insulae
and amygdala show less activation in ALS. These differences become stronger with
progression of the disease 6 months later.
Details are in the caption following the image
Figure 6
Open in figure viewer
PowerPoint

Local brain activation measured with fMRI to 60 affective slides with social
content. A: Twelve patients with ALS and 14 age-matched healthy controls at two
time points. B: Same group after 6 months of disease progression. Activations of
healthy controls subtracted from ALS. Activations in yellow-red indicate more
activation in ALS (Lulé et al., in press).
One is tempted to speculate that with progression of this fatal disease, emotional
responding on the behavioral and central nervous system level improves toward
positively valenced social cues, resulting in a more positive emotional state than
in healthy controls! The positive responding and positive interaction of the social
environment and caretakers to a fatally ill, paralyzed person may, in part, be
responsible for the prosocial emotional behavior and for the modified brain
representation of the “observer” depicted in Figure 6 as predicted by social
learning theory (Bandura, 1969). Taken together, the results on emotional
responding and quality of life in paralyzed ALS patients suggest a more cautious
and ethically more responsive approach toward hastened death decisions and last-
will orders of patients and their families. The data reported here also speak
pervasively for the usefulness and necessity of noninvasive BCI in ALS and other
neurological conditions leading to complete paralysis.

The preceding sections were devoted to BCIs designed for verbal communication in
completely paralyzed persons unable to use muscular or autonomic responses to
activate an assisted communication device. The second major field of BCI research
concerns restoration of movement in patients with paralysis, mostly spinal cord
lesions, chronic stroke, and other movement disorders. It is certainly an
attractive possibility to build a direct connection between voluntary movement
command centers in the brain and the periphery isolated from these regions by a
central, spinal, or peripheral lesion.
Invasive and Noninvasive BCIs for Restoration of Movement

Brain–computer interface research received its impetus from animal research

reconstructing movement from microelectrode-recorded spike trains or synaptic field
potentials (Donoghue, 2002; Nicolelis, 2001). After extensive training and the
implementation of learning algorithms (for an exception, where animals learned
rapidly, see Serruya et al., 2002), monkeys move cursors on screens toward targets
or an artificial hand moves in four directions directed by spike activity,
demonstrating the possibility of translating cellular activity into simple
movements online. After such training, even complex movement patterns can be
reconstructed from an astonishingly small number of cells located in the motor or
parietal areas (Musallam, Corneil, Greger, Scherberger, & Andersen, 2004;
Nicolelis, 2001; Schwartz et al., 2001; Taylor et al., 2002). The plasticity of the
cortical circuits allows learned control of movements directly from the cellular
activity even outside the primary or secondary homuncular representations of the
motor cortex (Taylor et al., 2002).

A multielectrode array recording spike and field potentials simultaneously was

implanted in a single quadriplegic patient's motor hand area (2004) by Donoghue's
group (personal communication, April 2005). Within a few training sessions, the
patient learned to use neuronal activity from field potentials to move a computer
cursor in several directions comparable to the tasks used for multidimensional
cursor movements in the noninvasive SMR-BCI reported by Wolpaw and McFarland
(2004). None of the invasive procedures allowed restoration of skillful movement in
paralyzed animals or people in everyday-life situations. The animals studied in BMI
research (Nicolelis, 2003) were all intact animals who learned to move an
artificial device or curser for food reward without moving their intact arm in
highly artificial laboratory situations. Any generalization from the invasive
animal BCI approach to paralyzed people is premature.

In contrast to the invasive approaches, SMR-controlled BCIs developed by

Pfurtscheller and colleagues (Pfurtscheller, Neuper, et al., 2003; Pfurtscheller et
al., 2005) allowed control of reaching and grasping in high spinal cord lesioned
patients. Pfurtscheller, who was the first in testing and implementing SMR-based
BCIs for motor paralysis, demonstrated convincingly the potential usefulness of
noninvasive BCIs for motor restoration, more clearly than the widely acclaimed and
cited animal experiments using implanted microelectrodes. In one preparation,
Pfurtscheller, Neuper, et al. (2003) used the SMR signals to activate electric
stimulation electrodes attached to the paralyzed arm and hand muscles in order to
reach and grasp objects in a quadriplegic patient. These data suggest that, with
intelligent prosthetic devices and orthoses, electrical muscle stimulation, and EMG
feedback from the target muscles, noninvasive BCIs may have promise for highly
complex movement reconstruction. Neuper, Müller, Kübler, Birbaumer, and
Pfurtscheller (2003) demonstrated successfully that the same SMR-based BCI used for
motor control can be used as a communication device in a paralyzed cerebral palsy
patient and that training and measurement may be performed even from laboratories
located at long distances from the patient. However, none of the paralyzed patients
reported in the literature is using the motor BCI in everyday-life situations as
long as voluntary upper face and shoulder movements can activate an artificial
limb. Therefore, in spinal cord lesioned patients, invasive and noninvasive BCIs
(BMIs) may be useful in the future for the few patients with extremely high spinal
cord lesions only.

Another obstacle for real-life daily use of BCIs regardless of the type of
application is their demand on attention. Whereas simple motor commands in the
intact adult organism are executed with a minimum of cognitive resource allocation,
the voluntary production of brain signals irrespective of the type of signal needs
more and continuous attentional resource mobilization than highly automatized
skills because automatization of brain control is slow and probably never complete
(Neumann et al., 2004). In addition, the noninvasive BCIs allow relatively
undisturbed slow verbal communication, but production of movement with brain
activity inevitably generates movement-related artifacts difficult to eliminate
online. Particularly in patients with spasticity and uncontrolled movement
episodes, attempts to produce motor action from EEG signals are often punished by
the presence of these artifacts and cause frustration and decline in motivation
(Birbaumer et al., 2003, 2004; Kübler, Winter, & Birbaumer, 2003). For these
special cases, the implantation of electrodes may constitute a viable alternative.
Whether the electrodes need to penetrate hundreds to thousands of neurons as some
maintain (Nicolelis, 2003) or only small samples of critically important neurons
responsible for directional tuning, for example, is an unresolved question.

Birbaumer, Weber, Buch, Neuper and Cohen (in press) at the National Institute of
Neurological Diseases and Stroke (NINDS) together with the Tübingen group (Lal et
al., 2006) developed a BCI system for chronic stroke that may solve most of the
problems of noninvasive BCIs devoted to motor restoration and may constitute a
sensitive alternative to invasive approaches. In this preparation, patients with no
residual hand movement are trained with a magnetoencophalography (MEG)-contolled
hand orthosis (Figure 7).
Details are in the caption following the image
Figure 7
Open in figure viewer
PowerPoint

BCI using sensorimotor magnetic field oscillations (CTF MEG 275 channels) for motor
restoration of paralyzed hand in chronic stroke. Top: Feedback curser at the screen
indicates amount of SMR present during 7 s; the goal at the right side of the
screen indicates whether the patient has to increase SMR (lower goal) or decrease
it (upper goal). The orthosis moves the hand proportional to the SMR changed
achieved. Bottom: Experimental situation in MEG with fingers fixed to the orthosis
opening and closing the hand.

For the first 10 to 20 training sessions in the MEG and after successful hand
opening, closing, and grasping using feedback and modulation of central SMR
magnetic-field oscillations, the patient is switched to a mobile EEG-SMR-based BCI
wearing the same orthosis. Because brain magnetic fields are not attenuated and
distorted on their way from the cortical generators to the MEG dewar containing the
recording SQUIDs, MEG provides a much larger and more localized SMR response,
allowing control of even single fingers (Braun, Schweizer, Elbert, Birbaumer, &
Taub, 2000). The head of the patient is fixated in the dewar and the fingers
attached to the orthosis open and close the hand contingent on SMR increase and
decrease. The patient receives visual and proprioceptive feedback from his/her own
movement and simultaneously watches a screen with an up or down moving cursor that
indicates the amount of SMR present in the appropriate cortical region 7 s before
the self-produced SMR moves the orthosis attached to the hand. Figure 8 depicts the
SMR magnetic field localization and training performance of a patient with long-
standing chronic stroke and complete immobility of the affected hand. As a positive
side effect, the patient experienced complete relief of hand spasticity after
several training sessions.
Details are in the caption following the image
Figure 8
Open in figure viewer
PowerPoint

Magnetic field SMR-BCI in a chronic stroke patient. Top: Magnetic field

distribution of 9 Hz magnetic SMR (yellow-brown) parietal, posterior of lesion,
ipsilesional. Bottom: Learning of SMR control in a chronic stroke patient over 11
sessions.

The primary aim of the MEG-BCI training in chronic stroke is not only restoration
of movement but cortical reorganization and compensatory cerebral activation of
nonlesioned brain regions through voluntary brain-controlled hand movement of the
paralyzed limb and reduction of contralesional hemispheric inhibition. Duque et al.
(2005), Murase, Duque, Mazzocchio, and Cohen (2004), and Ward and Cohen (2004) have
shown in a series of transcranial magnetic stimulation (TMS) experiments that the
strong inhibitory effect from the healthy hemisphere on the lesioned hemisphere may
be responsible for the lack of reorganization and insufficient recovery of the
stroke-affected brain area. Consequently, the MEG-BCI training is targeted toward a
“strenghthening” of the ipsilesional brain regions around the destroyed tissue and
“weakening” of the homotypical regions in the opposite hemisphere. This is achieved
by using SMR oscillations (from 10 to 20 Hz) as a movement-directing source
originating in the immediate neighborhood of the lesion and simultaneous
interruption of feedback and orthosis control with contralesional coactivation.
Cortical reorganization is measured before and after training with fMRI of imagined
and executed hand and lip movements as described by Lotze et al. (Lotze, Braun,
Birbaumer, Anders, & Cohen, 2003; Lotze, Grodd, et al., 1999; Lotze, Montoya, et
al., 1999). Whether the training results in improved hand mobility with or without
orthosis is the question of the ongoing clinical experiments. Chronic stroke with
no remaining finger mobility is resistant to treatment and shows no spontaneous
recovery; any improvement through BCI training therefore constitutes a success.
Again, invasive implantation of large quantities of electrodes with the many risks
and uncertainties involved may be superfluous or reserved for the few most
difficult cases.
Future Directions: The Metabolic Whole Brain BCI

Weiskopf et al. (2003) for the first time demonstrated convincingly that healthy
persons are able to regulate BOLD (blood oxygen level dependent) responses from
circumscribed cortical and subcortical brain regions using online functional
magnetic resonance imaging (fMRI-BCI). These authors and others (DeCharms et al.,
2005) demonstrated substantial effects of BOLD-response BCI training on behavior:
Pain, emotional arousal, and memory were investigated and astonishingly strong
effects on the behavioral variables after short training periods with fMRI-feedback
training were shown. This is not surprising, considering that vascular changes in
brain arteries and veins responsible for metabolic responses such as BOLD and brain
blood flow may allow superior voluntary (operant) control because of the vascular-
motor component of the physiological target response. Dilation and contraction of
vascular changes are sensed by the brain and regulated by neural structures with
closely coupled autonomic and somatic-motor functions, allowing access to voluntary
control (Dworkin, 1993).

The results presented by Weiskopf et al. (2004), Weiskopf, Klose, Birbaumer, and
Mathiak (2005), and Weiskopf, Scharnowski, et al. (2005) constitute the first step
in the application of fMRI-BCI to emotional disorders: fMRI allows anatomically
specific control of subcortical and cortical areas responsible for the regulation
of emotions not as accessible to electrophysiological methods as EEG and MEG such
as amygdala, limbic insular and cingulate regions, and anterior basal ganglia
(Figure 9).
Details are in the caption following the image
Figure 9
Open in figure viewer
PowerPoint

FMRI-BCI, experimental setup. Subject (brain in center) watches screen with yellow
line (left) representing BOLD response. Required increase of BOLD is indicated by
green bar, decrease by blue bar. Signals are processed in a 3 T Siemens Trio
Scanner (right) online using Brain Voyager (below right). Below left: Subject
receives feedback of the BOLD difference between two areas of interest (from
Weiskopf et al. 2004; Weiskopf, Veit, et al., 2005).

Clinical application of fMRI-BCI is presently unrealistic and unlikely, considering

the cost and technological difficulties involved in real-time fMRI. It will, at
present, remain reserved for research purposes and experiments intending to
demonstrate effects of learned local blood-flow changes on emotional and
motivational behavior. A clinically more realistic new metabolic BCI system has
been proposed and tested recently by Sitaram et al. (in press). These investigators
used near-infrared spectroscopy (NIRS) and measured, with optical recording
devices, changes in cortical oxygenation and deoxygenation. Using the reflection of
light in living tissues with high circulation density such as the brain, NIRS is
completely noninvasive (Coyle et al., 2004). NIRS devices are also relatively
inexpensive (price equivalent to that of a multichannel EEG) and commercially
available. Another virtue of NIRS is portability, allowing, for example, the
training of young children. Sitaram et al. (in press) demonstrated online operant
control of sensorimotor brain areas in five healthy subjects and spelling of
letters with NIRS-BCI with an accuracy of 70%–95% after only two training sessions
and with information transfer speed comparable to EEG-BCI.
Epilog

Brain–computer interfaces or brain–machine interfaces are intended to translate

“thought into action” with brain activity only. The research devoted to this goal
has raised many fascinating questions about brain–behavior relationships without
achieving its ultimate practical goals: communication with the completely paralyzed
and restoration of movement in paralysis. But the reformulation of the problem of
how brain cells and their output create observable behavior applied to an
existential problem of human suffering will focus the questions we ask in cognitive
neuroscience and psychophysiology. BCI research stimulates long-held hope and
expectation of thought and emotion detection and translation from brain states. And
true to the old Yiddish saying, “Fur lojter hofenung wer ich noch meschugge” [I am
crazy with hope].
REFERENCES
Citing Literature

Volume43, Issue6

November 2006
Pages 517-532

Figures
References
Related
Information

Recommended

30+ years of P300 brain–computer interfaces

Brendan Z. Allison, Andrea Kübler, Jing Jin
Psychophysiology

An auditory oddball (P300) spelling system for brain‐computer interfaces

A. Furdea, S. Halder, D.J. Krusienski, D. Bross, F. Nijboer, N. Birbaumer, A.
Kübler
Psychophysiology

A Brain–Computer Interface Controlled Auditory Event‐Related Potential (P300)

Spelling System for Locked‐In Patients
Andrea Kübler, Adrian Furdea, Sebastian Halder, Eva Maria Hammer, Femke
Nijboer, Boris Kotchoubey
Annals of the New York Academy of Sciences

Neuropsychological and neurophysiological aspects of brain‐computer‐interface

(BCI) control in paralysis
Ujwal Chaudhary, Natalie Mrachacz-Kersting, Niels Birbaumer
The Journal of Physiology

Download PDF
back
Additional links
About Wiley Online Library

Privacy Policy
Terms of Use
About Cookies

Accessibility
Wiley Research DE&I Statement and Publishing Policies
Developing World Access

Help & Support

Contact Us
Training and Support
DMCA & Reporting Piracy

Opportunities

Subscription Agents
Advertisers & Corporate Partners

Connect with Wiley

The Wiley Network

Wiley Press Room
Copyright © 1999-2023 John Wiley & Sons, Inc. All rights reserved
Wiley Home Page