PRESIDENTIAL ADDRESS, 2005

Breaking the silence: Brain–computer interfaces (BCI)

for communication and motor control

NIELS BIRBAUMERa,b

aInstitute of Medical Psychology and Behavioral Neurobiology, University of Tubingen, Tubingen, GermanybNational Institutes of Health, National Institute of Neurological Disorders and Stroke, Human Cortical Physiology, Bethesda, Maryland, USA

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 vari-

ations 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.

Descriptors: Brain–computer interface, Brain–machine interface, EEG, Invasive brain measures, Locked-in syndrome

A brain–computer interface (BCI) or brain–machine interface

(BMI) activates electronic or mechanical devices with brain ac-

tivity 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 inva-

sive from noninvasive BCIs: Invasive BCIs use activity recorded

by brain implanted micro- or macroelectrodes, whereas non-

invasive 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, Neu-

per, et al., 2003; Wolpaw, Birbaumer, McFarland, Pfurtscheller,

& Vaughan, 2002), (3) P300 and other event-related brain po-

tentials (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 re-

views 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 se-

quences in healthy animals; if they discuss clinical applications in

The author and his work are supported by the Deutsche Forschungs-

gemeinschaft (DFG) and the National Institutes of Health (NIH). The

editor, Bob Simons, made invaluable suggestions and corrections at all

stages of themanuscript’s preparation. The comments of two anonymous

reviewers, ofManyDonchin, AndreaKubler, Theresa Vaughan, and Jon

Wolpaw are greatly appreciated. The data frommy 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.Address reprint requests to: Niels Birbaumer, Ph.D., Institute of

Medical Psychology and Behavioral Neurobiology, MEG-Center, Uni-versity of Tubingen, Gartenstrasse 29, D-72074 Tubingen, Germany.E-mail: niels.birbaumer@uni-Tuebingen.de.

Psychophysiology, 43 (2006), 517–532. Blackwell Publishing Inc. Printed in the USA.Copyright r 2006 Society for Psychophysiological ResearchDOI: 10.1111/j.1469-8986.2006.00456.x

517

human patients at all, a science fiction perspective of whatmay be

possible is given without reference to the few published clinical

applications. The noninvasive BCI literature overviews (Kubler,

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:

1. What is the role of voluntary motor control and of the feed-

back 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 reorgan-

ization on behavior?

This review addresses these questions in the context of BCI re-

search 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 ‘‘Elek-

trenkephalogramm’’ (1929) about the possibility of reading

thoughts from the EEG traces by using sophisticated mathemat-

ical analyses. Grey Walter, the brilliant EEG pioneer who de-

scribed 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 re-

search traditions, though both have their roots in animal experi-

ments. Invasive BCIs consist of implantedmultielectrode grids in

the motor cortex of paralyzed patients (Donoghue, 2002), pre-

motor cortex of monkeys (Carmena et al., 2003), or parietal

motor command areas (Schwartz et al., 2001). They try to re-

construct intended skilled movements from neuronal firing pat-

terns 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 mon-

keys after extensive training of a reaching and grasping move-

ment that firing patterns of 32 neurons are sufficient to execute

that movement directly with an artificial limb. Chapin, Moxon,

Markowitz, andNicolelis (1999) trained rats tomove a lever with

an artificial arm in a Skinner box for reward with extracellular

firing of cortical cells without any actual movement. The neur-

onal firing pattern that used to precede and accompany the lever

pressing response alone was able to operate on the lever deliv-

ering 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 au-

tonomous nervous system (ANS) as autonomous and independ-

ent 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) condi-

tioning, a distinction first emphasized by Skinner (1953; Holland

& Skinner, 1961).

Miller presented experimental evidence in curarized and ar-

tificially ventilated rats showing that even after long-term cura-

rization of several weeks, the animals learned to increase and

decrease heart rate, renal blood flow, and dilation and constric-

tion of peripheral arteries in an operant conditioning paradigm

rewarding the animals for increases and decreases of these spe-

cific 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 fail-

ure, 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’ enthu-

siasm, 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. Fig-

ure 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 andmost 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.

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., inges-

tion of food restores glucostatic and fluid balance). In the cu-

rarized 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 be-

cause imbalances of the equilibrium do not occur.

The chronically curarized rat and the completely paralyzed,

artificially ventilated and fed locked-in patient share many simi-

larities; difficulties in communicating with these patients may be

understood based on these similarities.

518 N. Birbaumer

The difficulties in replicating the operant learning of auto-

nomic variables were accompanied by an ‘‘awakening’’ in the

clinical arena of biofeedback applications: The most impressive

clinical results were achievedwith electromyographic feedback in

chronic neuromuscular pain (Flor & Birbaumer, 1993), neuro-

muscular rehabilitation of various neurological conditions

(Birbaumer & Kimmel, 1979), particularly external spincter

control in enuresis end encopresis (Holzl & 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 (Holzl &Whitehead, 1983). It became

painfully clear that only very limited positive effects of bio-

feedback 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 pres-

ently called) were the self-regulation of brain waves (Kamiya,

1971). Increase and decrease of alpha frequency of the EEGwere

supposed to create ‘‘meditative’’ states with many beneficial ef-

fects 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 over-

view, see Rockstroh, Elbert, Birbaumer, & Lutzenberger, 1989).

Warning voices such as experiments byMulholland and his group

(Mullholland & Evans, 1966) demonstrating perfect control of

alphawaves throughmanipulation 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 or-

ganization of the motor and somatosensory cortical strip. Im-

agery 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 (Pfurtsc-

heller 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 in-

dicated 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 im-

portant to note that SMR is often called mu-rhythm following a

suggestion of Gastaut (Gastaut, 1952; Gastaut, Terzian, & Gas-

taut, 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 rec-

ommend that the term SMRas used by Sterman et al. be retained

because of its well-defined theoretical and experimental back-

ground.

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 ma-

nipulation (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:

1. Strong and anatomically specific effects of self-induced cor-

tical changes on behavior and cognition;

2. Solid neurophysiological evidence about anatomical sources

and physiological function of slow cortical potentials (for re-

views, 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

Breaking the silence 519

Figure 1. 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).

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 train-

ing sessions (Lutzenberger, Roberts, & Birbaumer, 1993). Sev-

eral clinical studies confirmed the critical importance of the

anterior brain systems for physiological regulation of CNS func-

tions: Lutzenberger et al. (1980) showed that patients with ex-

tended prefrontal lobe lesions were unable to learn SCP control

despite intact intellectual functioning. Disorders with prefrontal

dysfunctions such as attention deficit disorder (ADD; Birbau-

mer, Elbert, Rockstroh, & Lutzenberger, 1986) and schizophre-

nia (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 simultan-

eously during training.

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 de-

pends 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 acti-

vation thresholds and SCP in selective attention and motor

preparation. Braitenberg (Braitenberg & Schuz, 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-vol-

untary 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 ex-

tremely 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 re-

spiratory 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 com-

pletely 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.

520 N. Birbaumer

Figure 2. 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).

Based on the extensive knowledge and clinical experience ac-

quired 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 (Kubler, Kotchoubey, et al.,

2001; Kubler, Neumann, et al., 2001). After achievingmore than

70% control, letters or words are presented on a computer screen

or spoken by a word program. Patients select a letter by succes-

sively reducing letter strings containing the desired letter by cre-

ating SCPs after appearance of the desired letter (Birbaumer

et al., 1999; Birbaumer, Hinterberger,Kubler, &Neumann, 2003;

Kubler, 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 pa-

tients arrived at the locked-in state and were able to continue to

use the BCI. Seven additional patients began training after en-

tering 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 cog-

nitive 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, NewYork, 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 move-

ment 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 cov-

ering 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 Tubingen 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 fol-

low 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.

SCP-BCIs need more extensive training than other BCI

modes but may have the best stability and independence of sens-

ory, motor, and cognitive functioning necessary for its applica-

tion 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–Tubingen

group created aWeb 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 profes-

sional 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 at-

tractive 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’’ fash-

ion. From the published material, it is difficult to judge the use-

fulness 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 pa-

tients 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 dec-

ade. 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

Breaking the silence 521

prohibit their use formotor restoration ormotor neuroprosthesis

applications (Carmena et al., 2003; Taylor, Tillery, & Schwartz,

2002). This argument was recently countered experimentally by

Wolpaw and McFarland (2004), who demonstrated two-dimen-

sional 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).

522 N. Birbaumer

Figure 3. 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 ofmovement and imagery or execution ofmovement (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 redmoving 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).

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 ob-

served 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 (Kubler, Nijboer, et al., 2005). The incorpor-

ation ofmore sophisticated algorithms for EEG classification did

not improve the situation substantially (Hinterberger, Kubler,

Kaiser, Neumann, & Birbaumer, 2003; see results of the BCI

competition in the IEEE Transactions in Biomedical Engineer-

ing; 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 classifi-

cation algorithms (Hill et al., in press).

In humans, there are two published reports, in addition to the

alreadymentioned attempts by Pfurtscheller’s group, on invasive

BCIs with epileptic patients. In these experiments, subdural

macroelectrodes were implanted over frontal regions, and pa-

tients 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 Ma-

chines, SVM,were used as classification algorithms; see Lal et al.,

2004; Schroder 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 re-

jecting a letter by imagery of tongue movement (red field at cor-

tex of Figure 4).

This indicates, not surprisingly, that with subdurally implant-

ed macroelectrodes, degrees of freedom, precision of classifica-

tion, and success rates may substantially improve. The first

implantation of 100microelectrodes in themotor cortex of a high

spinal cord patient by Donoghue et al. (personal communica-

tion) 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 implant-

ation 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 im-

portant argument of patients was that time is not an issue if one is

completely paralyzed (Birbaumer et al., 1999, 2004; Kubler et al.,

2003; Kubler, 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 debili-

tating neurological diseases (subcortical stroke, Guillain Barre,

extensive brain damage). If patients, their families, and the local

ethical committees agree, implantations of micro- or macroelec-

trodes subdurally or in brain tissue should be considered. How-

ever, 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 im-

plantation is weak as long as the noninvasive BCIs are available

Breaking the silence 523

Figure 4. 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 100Hz. Red shows the classification for tongue imagery, green for finger projected on the cortical surface of

the same patient.

and functioning. The slow spelling speed and high error rate (even

in highly trained patients rarely above 80% trials correct) of non-

invasive EEG-based BCIs is well tolerated by paralyzed patients

with adifferent life perspective and anurgent 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 sta-

bile communication (n5 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 commu-

nication in the complete locked-in state assumes that with pro-

gression of ALS or Guillain-Barre 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 neuropsy-

chological 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 com-

plex 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 pa-

tient 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 pa-

tients 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 some-

times 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 oftendifficult to decidewhether the patient

is awake or in sleep stage 1 or 2. One CLIS patient gave informed

consent to implantationof 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 informa-

tion 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 com-

munication, 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 (SMRdecrease 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 extin-

guished.

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 con-

scious 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 intomeaningful

percepts; its absence seems incompatible with conscious percepts

and ‘‘Gestalt’’ formation (Kaiser, Lutzenberger, Preissl, Acker-

mann, & Birbaumer, 2000). Psychophysiological and psycho-

physical 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. Vol-

untary action and thoughts and their consequences are attracted

together in time; involuntary externally initiated and attributed

responses and their effects are experienced asmore 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 ca-

pacities remain unclear until the first CLIS patient communicates.

Under the assumption that passive-sensory information pro-

cessing 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 re-

warding or punishing stimulus (i.e., attention from others for

that thought) creates an extension of the subjective time percep-

tion 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

524 N. Birbaumer

between them. With the lack of reinforcing contingencies con-

trolling the maintenance of the stream of thoughts, they extin-

guish slowly. As demonstrated by Haggard et al. (2002), it is this

lack of motor control consisting of intention (‘‘will’’), prepar-

ation, execution, and sensory and external feedback that deter-

mines 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 de-

pression at the affective level and deficits in problem solving at

the cognitive level (Seligman, 1975). Surprisingly, the common-

sense prediction that complete paralysis accompanied by the loss

of most positive reinforcers should result in depression and des-

pair 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 eu-

thanasia 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 sup-

port 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 usu-

ally enjoy a good meal,’’ ‘‘I like to see a beautiful sunset’’). Spe-

cial instruments had to be developed for this population (Kubler,

Winter, et al., 2005). In studies by Breitbart, Rosenfeld, and

Penin (2000) and by our group (Kubler,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 depres-

sion (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 asmuch

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 has-

tened death.

It could be argued that questionnaires and interviews reflect

more social desirability and social pressure than the ‘‘real’’ be-

havioral–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 posi-

tive attitude in these groups. This hypothesis is strongly sup-

ported 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). Lule et al. (2005) and

Lule 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. Evenmore 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 dis-

ease 6 months later.

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 per-

son may, in part, be responsible for the prosocial emotional be-

havior 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 an-

imal research reconstructing movement from microelectrode-

recorded spike trains or synaptic field potentials (Donoghue,

2002; Nicolelis, 2001). After extensive training and the imple-

mentation 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

Breaking the silence 525

moves in four directions directed by spike activity, demonstrating

the possibility of translating cellular activity into simple move-

ments online. After such training, even complex movement pat-

terns 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 hom-

uncular 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

526 N. Birbaumer

Figure 5. Depression and quality of life in ALS. A: Depressionmeasured with amodified 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 Kubler, Nijboer, et al., 2005.)

motor hand area (2004) by Donoghue’s group (personal com-

munication, April 2005). Within a few training sessions, the pa-

tient 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 non-

invasive 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 situ-

ations. 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, Neu-

per, et al., 2003; Pfurtscheller et al., 2005) allowed control of

reaching and grasping in high spinal cord lesioned patients. Pfu-

rtscheller, 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 experi-

ments using implanted microelectrodes. In one preparation,

Pfurtscheller, Neuper, et al. (2003) used the SMR signals to ac-

tivate 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, Muller, Kubler, 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 measure-

ment may be performed even from laboratories located at long

distances from the patient. However, none of the paralyzed pa-

tients reported in the literature is using the motor BCI in every-

day-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 exe-

cuted with a minimum of cognitive resource allocation, the vol-

untary production of brain signals irrespective of the type of

signal needs more and continuous attentional resource mobil-

ization 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 slowverbal communication, but production ofmove-

ment 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; Kubler, Winter, &

Birbaumer, 2003). For these special cases, the implantation of

electrodes may constitute a viable alternative. Whether the elec-

trodes need to penetrate hundreds to thousands of neurons as

some maintain (Nicolelis, 2003) or only small samples of

Breaking the silence 527

Figure 6. 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 (Lule et al., in press).

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 Tubingen 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 restor-

ation and may constitute a sensitive alternative to invasive ap-

proaches. In this preparation, patients with no residual hand

movement are trained with a magnetoencophalography (MEG)-

contolled hand orthosis (Figure 7).

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 attenu-

ated and distorted on their way from the cortical generators to

the MEG dewar containing the recording SQUIDs, MEG pro-

vides a much larger and more localized SMR response, allowing

control of even single fingers (Braun, Schweizer, Elbert, Birbau-

mer, & 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 SMRmagnetic field localization and training performance of

a patient with long-standing chronic stroke and complete im-

mobility of the affected hand. As a positive side effect, the patient

experienced complete relief of hand spasticity after several train-

ing 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 re-

528 N. Birbaumer

Figure 7. BCI using sensorimotormagnetic field oscillations (CTFMEG

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 inMEGwith fingers fixed to the orthosis

opening and closing the hand.

Figure 8. 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.

gions through voluntary brain-controlled hand movement of the

paralyzed limb and reduction of contralesional hemispheric in-

hibition. 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 re-

organization and insufficient recovery of the stroke-affected

brain area. Consequently, the MEG-BCI training is targeted to-

ward 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 os-

cillations (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 ques-

tion 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 uncertain-

ties 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 convin-

cingly 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 be-

cause 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, Schar-

nowski, 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 electro-

physiological methods as EEG and MEG such as amygdala,

limbic insular and cingulate regions, and anterior basal ganglia

(Figure 9).

Clinical application of fMRI-BCI is presently unrealistic and

unlikely, considering the cost and technological difficulties in-

volved in real-time fMRI. It will, at present, remain reserved for

research purposes and experiments intending to demonstrate ef-

fects of learned local blood-flow changes on emotional and mo-

tivational behavior. A clinically more realistic new metabolic

BCI system has been proposed and tested recently by Sitaram

et al. (in press). These investigators usednear-infrared spectroscopy

(NIRS) andmeasured, 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. An-

other 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 informa-

tion transfer speed comparable to EEG-BCI.

Epilog

Brain–computer interfaces or brain–machine interfaces are in-

tended to translate ‘‘thought into action’’ with brain activity

only. The research devoted to this goal has raised many fascin-

ating 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 prob-

lem of human suffering will focus the questions we ask in cog-

nitive neuroscience and psychophysiology. BCI research

stimulates long-held hope and expectation of thought and emo-

tion detection and translation from brain states. And true to the

old Yiddish saying, ‘‘Fur lojter hofenung wer ich noch mes-

chugge’’ [I am crazy with hope].

Breaking the silence 529

Figure 9. 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).

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(Received March 30, 2006; Accepted July 11, 2006)

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