IEEE REVIEWS IN BIOMEDICAL ENGINEERING, VOL.

2, 2009 187

Clinical Applications of Brain–Computer Interfaces:

Current State and Future Prospects
Joseph N. Mak, Member, IEEE, and Jonathan R. Wolpaw

Clinical Application Review

Abstract—Brain–computer interfaces (BCIs) allow their users to time, a brain signal is translated into output commands that ac-
communicate or control external devices using brain signals rather complish the desire of the user. The most common example of
than the brain’s normal output pathways of peripheral nerves and use of such technology is the direct control of a computer cursor
muscles. Motivated by the hope of restoring independence to se-
verely disabled individuals and by interest in further extending by a person or animal using a BCI based on electrophysiolog-
human control of external systems, researchers from many fields ical signals.
are engaged in this challenging new work. BCI research and devel- A BCI allows a person to communicate with or control the
opment has grown explosively over the past two decades. Efforts external world without using conventional neuromuscular path-
have begun recently to provide laboratory-validated BCI systems
to severely disabled individuals for real-world applications. In this
ways. That is, messages and control commands are delivered not
paper, we discuss the current status and future prospects of BCI by muscular contractions but rather by brain signals themselves.
technology and its clinical applications. We will define BCI, review This BCI feature brings hope to individuals who are suffering
the BCI-relevant signals from the human brain, and describe the from the most severe motor disabilities, including people with
functional components of BCIs. We will also review current clin- amyotrophic lateral sclerosis (ALS), spinal-cord injury, stroke,
ical applications of BCI technology and identify potential users and
potential applications. Lastly, we will discuss current limitations of and other serious neuromuscular diseases or injuries. BCI tech-
BCI technology, impediments to its widespread clinical use, and ex- nology holds promise to be particularly helpful to people who
pectations for the future. are “locked in”—cognitively intact but without useful muscle
Index Terms—Augmentative communication, brain–computer function. Restoration of basic communication capabilities for
interface (BCI), conditioning, electroencephalography (EEG), mu these people would significantly improve their quality of life as
rhythm, P300, rehabilitation, sensorimotor cortex. . well as that of their caregivers, increase independence, reduce
social isolation, and potentially reduce cost of care [1].
BCI research has undergone an explosive growth in recent
I. INTRODUCTION
years. At present, there are more than 400 groups worldwide
HE possibility of establishing a direct communication and engaging in a wide spectrum of research and development pro-
T control channel between the human brain and computers
or robots has been a topic of scientific speculation and even sci-
grams, using a variety of brain signals, signal features, and anal-
ysis and translational algorithms [2]. In this paper, we discuss
ence fiction for many years. Over the past 20 years, this idea the current status and future prospects of BCI technology and its
has been brought to fruition by numerous research and develop- clinical applications. We will define BCI, review the BCI-rele-
ment programs, and has evolved into one of the fastest growing vant source signals from the human brain, and describe the func-
areas of scientific research. This technology, called brain–com- tional components of BCIs. We will also review current clinical
puter interface (BCI) technology, provides a new output channel applications of BCI technology and identify potential users and
for brain signals to communicate or control external devices potential applications. Lastly, we will discuss current limitations
without using the normal output pathways of peripheral nerves of BCI technology, impediments to its widespread clinical use,
and muscles. A BCI recognizes the intent of the user through the and expectations for the future.
electrophysiological or other signals of the brain. Electrophysi-
ological signals may be recorded over the scalp, underneath the
scalp, or within the brain; other types of physiological signals II. BCI DEFINITION, SIGNAL TYPES, AND OPERATION
may be recorded by magnetic sensors or other means. In real
A. Definition of a BCI
Manuscript received August 15, 2009; revised September 24, 2009. Current
version published December 01, 2009. This work was supported by the National A brain–computer interface , also sometimes referred to as
Institutes of Health under Grants HD30146 (NCMRR/NICHD) and EB00856 a brain–machine interface, is a communication and/or control
(NIBIB and NINDS)), the James S. McDonnell Foundation, the NEC Founda-
tion, the Altran Foundation, the ALS Hope Foundation, and the Brain Commu- system that allows real-time interaction between the human
nication Foundation. brain and external devices. A BCI user’s intent, as reflected
The authors are with the Laboratory of Neural Injury and Repair, Wadsworth by brain signals, is translated by the BCI system into a de-
Center, New York State Department of Health, Albany, NY 12201-0509 USA
(e-mail: jmak@wadsworth.org; wolpaw@wadsworth.org). sired output: computer-based communication or control of an
Digital Object Identifier 10.1109/RBME.2009.2035356 external device.
1937-3333/$26.00 © 2009 IEEE

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188 IEEE REVIEWS IN BIOMEDICAL ENGINEERING, VOL. 2, 2009

The term “brain–computer interface” was first introduced by (EEG), cortical surface (ECoG), and intracortical recording
the pioneering work of Vidal [3], [4] in the early 1970s. Moti- devices. Each of the recording methods has its own advantages
vated by the hope of creating an alternative output pathway for and disadvantages. EEG signals are recorded from the scalp.
severely disabled individuals and an interest in further extending Since EEG-based BCIs are noninvasive, they provide the
human direct control of external systems, BCI researchers have simplest and safest BCI recording methods. However, EEG
engaged in this new challenging work. Researchers hail from a has limited frequency range and spatial resolution, and it is
large variety of fields, including clinical neurology and neuro- more susceptible to powerline interference and other artifacts
surgery, rehabilitation engineering, neurobiology, engineering, like electromyographic (EMG) signals from cranial muscles
psychology, computer science, and mathematics, and have led or electrooculographic (EOG) activity. Fig. 1(a) shows two
an explosive growth in BCI research and development over the noninvasive BCI systems based on different EEG signal fea-
past two decades [3], [5]–[22]. tures. Electrocorticographic (ECoG) signals are recorded from
A BCI is defined as a system that measures and analyzes brain electrodes surgically placed on the surface of the cortex. These
signals and converts them in real time into outputs that do not electrodes measure the same signals as in EEG, but their closer
depend on the normal output pathways of peripheral nerves and proximity to the brain and the elimination of the insulating
muscles [23]. Systems that measure electrical activity gener- features of the skull and dura result in greater signal amplitude,
ated by muscles do not satisfy the above definition, and there- wider detectable frequency range, and better topographical
fore are not BCIs. Systems that measure brain activity that de- resolution. Fig. 1(b) shows an example of human ECoG signals
pends on muscle control are not pure, or independent BCIs, but and topographies during two-dimensional movement con-
might rather be called dependent BCIs. Thus, for example, a trol. Finally, intracortical methods can be used for a BCI by
system that uses visual evoked potentials (VEPs) to detect gaze recording local field potentials (LFPs) and neuronal action po-
direction [24], [25] is a dependent BCI because it requires neu- tentials (spikes). These intracortical methods represent the most
romuscular control of eye (or head) movements. (It should be invasive BCI methods since they record electrical activity from
noted that several recent studies [26]–[28] indicate that some electrodes implanted in the brain. Fig. 1(c) shows a microelec-
VEP-based BCI systems are not totally dependent on gaze di- trode array for intracortical recording, its placement location in
rection, and thus are to a limited degree independent.) human motor cortex, and results from intracortical BCI studies
BCIs do not read minds. Rather, a BCI changes electro- in monkeys. Both ECoG and intracortical recordings provide
physiological signals from mere reflections of central nervous wider frequency range, higher topographical resolution, and
system (CNS) activity into messages and commands that act on better signal quality and dimensionality than EEG. However,
the world and that, like output in conventional neuromuscular both methods require surgery, and issues such as risk of tissue
channels, accomplish the person’s intent. Thus, a BCI replaces damage and infection and long-term recording stability arise
nerves and muscles and the movements they produce with [18], [30]. It remains possible that intracortical recording might
hardware and software that measure brain signals and translate not produce speed and accuracy of performance substantially
those signals into actions [14]. greater than what can be achieved with EEG, a noninvasive
Successful BCI operation depends on the interaction of two method not requiring surgery or any of its attendant risks [31].
adaptive controllers: the user, who produces specific brain sig- The comparative merits of noninvasive (EEG) methods and
nals that encode intent, and the BCI, which translates these sig- invasive (ECoG and intracortical) methods remain unresolved
nals into output that accomplishes the user’s intent. Aiming at present. With each method’s having its strengths and weak-
to replace the conventional neuromuscular output channels, a nesses, the decision of a potential BCI user for one method
BCI must function as an adaptive closed-loop control system. over the other may ultimately depend on the overall goal of the
It must provide real-time feedback to the user, by which the individual’s BCI use [32].
user can fine-tune the brain signals in order to optimize the de- Most studies of BCI clinical applications in humans have
sired output. It should be noted that a system that simply records been performed with EEG-based BCIs. These have shown that
and analyzes brain signals and does not provide the results of EEG-based BCIs can allow a person to control a computer
the analysis to the user in a real-time interactive way is not a cursor in at least three dimensions, to select letters to perform
BCI [29]. word-processing, to run computer-based Windows programs,
and to perform environmental control. Several people severely
B. Types of Brain Signals disabled by ALS have begun using the Wadsworth Center’s
In principle, a variety of neurophysiologic signals reflecting EEG-based BCI at home for everyday, independent use [33].
in-vivo brain activities might be recorded and used to drive a Human ECoG studies have been performed with volunteers
BCI. Depending on the biophysical nature of the signal source, who are under evaluation for epilepsy surgery. Prior to surgery,
these signals can be broadly grouped into three categories: elec- the neurosurgeons evaluate the patient’s brain activity using an
trophysiological, magnetic, and metabolic. array of ECoG electrodes to localize critical cortical functions
[16], [20], [34], [35]. If a patient volunteers, a BCI researcher
C. Electrophysiological Signals can perform BCI studies during the patient’s evaluation period,
Electrophysiological signals resulting from brain activity can which usually lasts only one or two weeks. Thus, the avail-
be broadly classified according to the degree of invasiveness ability of ECoG research subjects is somewhat limited and
of the recording device [30]. Fig. 1 illustrates BCI systems is always secondary to the clinical needs of the patients [36].
based on electrophysiological signals measured by noninvasive Moreover, the location of the ECoG electrode array is based

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MAK AND WOLPAW: CLINICAL APPLICATIONS OF BRAIN–COMPUTER INTERFACES 189

Fig. 1. (a) EEG-based BCI systems: i) Sensorimotor rhythm (SMR) BCI [83], [109]. EEG activity is recorded over the sensorimotor cortex. Users are trained to
control the amplitude of the  rhythm (8–12 Hz) or the  rhythm (18–26 Hz) in order to move a computer cursor to a top target or a bottom target on a computer
screen. Frequency spectra for vertical cursor movement (top or bottom target) indicate that the user’s control focuses in the -rhythm frequency band. Sample EEG
traces (bottom) show that the  rhythm is prominent with top targets and minimal with bottom targets. An SMR BCI can provide two- or even three-dimensional
movement control. (Adapted from [136] with permission from IEEE.) ii) P300 event-related potential BCI [5], [19]. A matrix of possible selections is shown on a
computer screen. EEG activity is recorded over the centroparietal cortex while these selections flash in succession. Only the selection desired by the user elicits a
P300 potential (e.g., a positive voltage deflection about 300 ms after the flash). (Adapted from [11] with permission from the Institute of Electrical and Electronics
Engineers.) (b) ECoG-based BCI systems: sample topographies of vertical and horizontal control using ECoG signals. These topographies show the color-coded
correlation (i.e., r values) of the cortical activity with vertical or horizontal movement. The level of task-related control of different cortical areas is indicated.
Actual and imagined tongue movements were used for vertical control, while actual and imagined hand movements were used for horizontal control. The traces
below each topography show r values for the locations (stars) used online. The frequency bands used online are indicated by yellow bars. Actual and imagined
tasks presented similar activity patterns over locations active with motor and motor imagery tasks. (Adapted from [20] with permission from the Institute of Physics
Publishing.) (c) Intracortical-based BCI systems. Top left: example of a 100-microelectrode array for chronic implantation in human motor cortex to record neuronal
action potentials and/or local field potentials. Top right: placement of an electrode array in the human motor cortex (arrow). (Adapted from [18] with permission from
Macmillan Publisher Ltd.) Bottom: three-dimensional cursor movements by groups of individual neurons in the motor cortex of a monkey. (Left) Average correlation
of the firing rate of a single cortical neuron with target direction over daily training sessions. (Right) Resulting improvement in BCI performance, measured as the
mean target radius required to maintain a 70% target hit rate. The size of the target needed decreased as the correlations of the firing rates of the neurons controlling
cursor movement with the target direction increased. (Reproduced from [13] with permission from the American Association for the Advancement of Science.)

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190 IEEE REVIEWS IN BIOMEDICAL ENGINEERING, VOL. 2, 2009

solely on the patient’s clinical needs, and thus might not equipment and the technical difficulties involved [76]. Further-
include cortical regions associated with brain patterns useful more, the BOLD response is a relatively low-frequency signal
for BCI [37]. Despite these obstacles, impressive results have ( 1 Hz) compared to EEG or MEG, and this limits its BCI
emerged from short-term ECoG studies, focusing mainly on information-carrying capacity. At present, MEG and fMRI’s
the capacities of ECoG signals for use in a human BCI [16], use remains reserved for identification of function-specific foci
[20], [34], [35], [38]–[48]. Most intracortical BCI data to date for subsequent placement of cortical electrodes [60], for reha-
have been obtained from animals, primarily from monkeys bilitation training of patients, and for other non-BCI research
[45]–[52]. While monkeys have been shown to be able to purposes.
use intracortical signals to control a robotic arm, comparable Near-infrared spectroscopy, which also measures blood oxy-
human data are very limited [8], [18], [49]. Due to the present genation, is another potential BCI method. In NIRS, light in the
practical limitations on invasive BCI studies in humans, BCI near infrared range (700–100 nm) [73] tracks neural metabo-
clinical applications to date have used primarily scalp-recorded lism by monitoring the relative amounts of oxyhemoglobin and
EEG signals. deoxyhemoglobin. An inrush of oxygen-rich blood occurs in an
active area and in surrounding tissue [70]. Thus far, NIRS-based
D. Magnetic and Metabolic Signals BCIs have not matched the performance of EEG-based BCIs
Magnetoencephalography (MEG) was recently proposed as [67]. Nevertheless, they are promising because, unlike fMRI and
a potential new source of brain-derived signals to operate a MEG, NIRS is inexpensive and portable [65], [67]–[69]. Thus,
BCI [50]–[53]. MEG is attractive because it is noninvasive, NIRS BCI methods might be of practical value for clinical ap-
able to detect frequency ranges above those available in EEG plications in the near future.
recordings [54], and has slightly higher spatial resolution than
EEG [55]. MEG measures very small magnetic fields produced E. BCI Operation
by the electrical activity of the brain [56]. Researchers have Any BCI, regardless of its recording methods or applications,
explored the potential of MEG BCI in the rehabilitation of consists of four essential elements, as described by Wolpaw
stroke patients with encouraging initial results [17], [50]. [14]: signal acquisition, feature extraction, feature translation,
Recent BCI research using MEG signals demonstrated reli- and device output. Fig. 2 illustrates the essential elements and
able self-control of sensorimotor rhythm amplitude [51] and operation of a BCI system, as well as its clinical applications.
satisfactory two-dimensional BCI control [53]. Despite its These four elements are managed through the system’s oper-
wider frequency range and excellent spatiotemporal resolution, ating protocol. Since BCIs based on electrophysiological sig-
MEG currently requires bulky and expensive equipment and a nals are in the most advanced state of development and have re-
protected environment, and thus is at present impractical for sulted in some clinical applications, the remainder of this paper
widespread clinical use [30]. focuses on BCIs of this type.
In recent years, there has been growing interest in BCIs
based on metabolic signals derived from the brain [57]–[69]. F. Signal Acquisition
Metabolic activity is assessed by measuring blood oxygenation
[the blood oxygen level dependent (BOLD) response] through Signal acquisition is the measurement of the neurophysio-
functional magnetic resonance imaging (fMRI) or near-infrared logic state of the brain. In BCI operation, the recording interface
spectroscopy (NIRS). These measures are known to be corre- (i.e., electrodes, for electrophysiological BCI systems) tracks
lated with neural activity in the brain [17], [70]–[72]. They take neural information reflecting a person’s intent embedded in the
advantage of the fact that during mental activation there is an in- ongoing brain activity. As discussed in the last section, the most
crease in oxyhemoglobin and a decrease in deoxyhemoglobin. common electrophysiological signals employed for BCI sys-
Weiskopf et al. [63] showed that a person can control the tems include EEG recorded by electrodes on the scalp, ECoG
fMRI BOLD response from circumscribed cortical and subcor- recorded by electrodes placed beneath the skull and over the
tical regions. Studies have repeatedly demonstrated that there cortical surface, and local field potentials (LFPs) and neuronal
is a tight correlation between voluntary changes in brain me- action potentials (spikes) recorded by microelectrodes within
tabolism and behavior (for review, see [73]). Benefiting from brain tissue. The brain electrical signals used for BCI operation
fMRI’s high spatial resolution and recent advances in simul- are acquired by the electrodes, amplified, and digitized.
taneous acquisition, analysis, and visualization of whole brain
G. Feature Extraction
images, researchers have successfully trained human subjects to
volitionally control localized brain regions using feedback from The signal-processing stage of BCI operation occurs in two
a real-time fMRI BCI (for complete review, see [74] and [75]). steps. The first step, feature extraction, extracts signal features
Furthermore, recent work by Lee et al. [59] has demonstrated that encode the intent of user. In order to have effective BCI op-
the possibility of two-dimensional real-time control of a robotic eration, the electrophysiological features extracted should have
arm through a motor imagery task by human subjects, using an strong correlations with the user’s intent. The signal features ex-
fMRI-based BCI. tracted can be in the time domain or the frequency domain [5],
Despite the above-mentioned outstanding features of MEG [11], [49], [77]–[80], or both [81]. The most common signal
and fMRI in acquiring valuable neural information from the features used in current BCI systems include amplitudes or la-
brain, their clinical application in BCI systems for real-life daily tencies of event-evoked potentials (e.g., P300), frequency power
use is currently not realistic, due to the high cost and size of the spectra (e.g., sensorimotor rhythms), or firing rates of individual

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MAK AND WOLPAW: CLINICAL APPLICATIONS OF BRAIN–COMPUTER INTERFACES 191

Fig. 2. Essential elements and operation of a BCI system. (Modified from [14] and [36] with permission from Elsevier and Wolters Kluwer, respectively.) Brain
signals that carry the intent of the user are first acquired by electrodes placed on the scalp (EEG), beneath the skull and over the cortical surface (ECoG), or
within brain tissue (intracortical). These brain signals are digitized, and specific signal features are extracted. The extracted signal features are translated into
device commands that activate and control assistive technology used for communication (e.g., spelling on a computer screen); movement control (e.g., robotic
arm) [Credit: Copyright Fraunhofer IPA)]; environmental control (e.g., TV, light, temperature, etc); locomotion (e.g., electric wheelchair); or neurorehabilitation.
(Adapted from [129] with permission from the Journal of Rehabilitation Research and Development.)

cortical neurons. An algorithm filters the digitized data and ex- the continuing changes of the signal features and to ensure that
tracts the features that will be used to control the BCI. In this the possible range of the specific signal features from the user
step, confounding artifacts (such as 60-Hz noise or EMG ac- covers the full range of device control [14], [82], [83].
tivity) are removed to ensure accurate measurement of the brain
signal features. I. Device Output
The signal features thus extracted and translated provide the
H. Feature Translation output to operate an external device. The output might be used to
The second step of signal processing is accomplished by the operate a spelling program on a computer screen through letter
translation algorithm, which converts the extracted signal fea- selection [5], [11], to move a cursor on a computer screen [12],
tures into device commands. Brain electrophysiological features [84], [85], to drive a wheelchair [86], [87] or other assistive
or parameters are translated into commands that will produce devices [88], to manipulate a robotic arm [89], [90], or even to
output such as letter selection, cursor movement, control of a control movement of a paralyzed arm through a neuroprosthesis
robot arm, or operation of another assistive device. A transla- [15], [91]. At present, the most commonly used output device is
tion algorithm must be dynamic to accommodate and adapt to the computer screen, and it is used for communication.

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192 IEEE REVIEWS IN BIOMEDICAL ENGINEERING, VOL. 2, 2009

J. Operating Protocol The third and largest group of potential BCI users consists of
people who retain substantial neuromuscular control. For most
The operating protocol determines the interactive functioning
in this group, present-day BCI systems, with their limited ca-
of the BCI system. It defines the onset/offset control, the de-
pacities, have little to offer. These individuals are usually much
tails of and sequence of steps in the operation of the BCI, and
better served by conventional technology. Nevertheless, some
the timing of BCI operation. It defines the feedback parameters
in this group, such as those with high-cervical spinal-cord in-
and settings, and possibly also any switching between different
juries, may prefer a BCI over conventional assistive devices that
device outputs. An effective operating protocol allows a BCI
coopt their remaining voluntary muscle control (e.g., systems
system to be flexible, serving the specific needs of an individual
that depend on gaze direction or EMG from facial muscles). In
user. At present, since most BCI studies occur in laboratories
the future, as the capacities, reliability, and convenience of BCI
under controlled conditions [1], investigators typically control
systems continue to improve, more people in this group could
most of the parameters in the protocol, providing simple and
find them of value, and the number of people using BCIs could
limited functionality to the BCI user. More flexible and com-
substantially increase.
plete operating protocols will be important for BCI use in real
The different conditions mentioned above impair the CNS in
life, outside of the laboratory.
different ways, and different BCIs depend on different aspects
of brain activity. Thus, some people may be better served by
III. BCI CLINICAL APPLICATIONS one BCI than by another. For example, people who have senso-
rimotor cortex impairment due to severe cerebral palsy may not
A. Potential BCI Users be able to use BCIs based on EEG or single-neuron activity from
Individuals who are severely disabled by disorders such as these cortical areas. In such people, BCI systems that use other
ALS, cerebral palsy, brainstem stroke, spinal-cord injuries, mus- EEG components (e.g., P300 [5], [11], [19], [92]) or neuronal
cular dystrophies, or chronic peripheral neuropathies might ben- activity from other brain regions might be good alternatives.
efit from BCIs. To help determine the value of BCIs for dif-
ferent individuals, Wolpaw et al. [30] suggested that potential B. Possible BCI Uses
BCI users be categorized by the extent, rather than the etiology, It is important to distinguish between a BCI and its appli-
of their disability. Evaluated in this way, potential BCI users fall cations [23]. The term BCI refers to the system that records,
into three reasonably distinct groups: 1) people who have no de- analyzes, and translates the input (i.e., the user’s brain signals)
tectable remaining useful neuromuscular control and are thus into device commands. In contrast, the term application refers to
totally locked-in; 2) people who retain only a very limited ca- the specific purposes or devices to which the output commands
pacity for neuromuscular control such as weak eye movements are applied. Recent focus on the real-world applications of BCI
or a slight muscle twitch; and 3) people who still retain sub- technology [93], [94] is speeding the transition of BCI research
stantial neuromuscular control and can readily use conventional from the laboratory to clinical products useful in everyday life.
muscle-based assistive communication technology. Although BCI applications could conceivably be clinical or non-
It is not yet clear to what extent BCIs can serve people in the clinical (e.g., computer games), this paper discusses clinical ap-
first group, those who are totally locked-in (e.g., by late-stage plications only.
ALS or severe cerebral palsy). Resolution of this issue requires The potential clinical uses of BCIs can be classified as 1) di-
extensive and prolonged evaluation of each individual in order rect control of assistive technologies and 2) neurorehabilitation.
to resolve basic issues of alertness, attention, visual or auditory Since the BCI serves as a replacement of normal neuromus-
capacities, and higher cortical function. While it has been hy- cular pathways, the most obvious BCI applications are those
pothesized that the totally locked-in state constitutes a unique that activate and control assistive technologies that are already in
BCI-resistant condition [17], the issue remains unresolved at place to enable communication and control of the environment.
present. It is worth mentioning that researchers have speculated These applications of BCIs to assistive technology encompass
that individuals in this group might be able to retain the capacity the areas of communication, movement control, environmental
for BCI use if they begin it before becoming totally locked-in control, and locomotion. The possible uses of BCIs in neurore-
[17], [30]. habilitation have just begun to be explored [29], [73].
At present, people in the second group constitute the pri-
mary prospective user population for current BCI systems. This C. Communication
group, which outnumbers the first group, includes people with Communication for people who are “locked in” probably rep-
late-stage ALS patients who rely on artificial ventilation as their resents the most pressing area in need of intervention with BCI
disease progresses, people with brainstem strokes, and people technology [93], [95]. Although other applications are under de-
with severe cerebral palsy. Typically, they retain only very lim- velopment, restoring communication has been the main focus of
ited, easily fatigued, and/or unreliable eye movements or other the BCI research community to date [83], [96], [97].
minimal muscle function and thus cannot be adequately served Distinguished from one another by the specific electro-
by conventional muscle-based assistive communication tech- physiological features measured, three types of EEG-based
nology. For people in this group, BCI systems may be able BCI systems have been tested in human subjects for the pur-
to provide basic communication and control that is more con- pose of communication—specifically, those based on 1) slow
venient and reliable than that provided by conventional tech- cortical potentials (SCPs), 2) P300 event-related potentials,
nology [30]. and 3) sensorimotor rhythms (SMRs). Both the SCP BCI and

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MAK AND WOLPAW: CLINICAL APPLICATIONS OF BRAIN–COMPUTER INTERFACES 193

the SMR BCI require significant training of the users to gain are visual and are based on the P300 speller first developed by
sufficient control of their brain activity to produce signals that Donchin et al. [11], [112]. In this BCI, the user faces a 6 6
can be effectively applied to BCI use. In contrast, a P300 BCI matrix of letters, numbers, symbols, and/or function keys. The
measures the brain’s response to stimuli (visual or auditory) of rows and columns in the matrix flash in a random order, and
special significance and requires minimal user training. the user attends to the matrix item s/he wishes to select. By de-
SCPs are slow voltage changes in cortex. They occur over tecting the row and column that elicit the largest P300, the BCI
0.5–10.0 s and are among the lowest frequency features of EEG. recognizes the user’s target letter/symbol. Because the P300 re-
Negative shifts of SCPs represent cortical activation associated sponse occurs normally, use of a P300 BCI does not require sub-
with movement or other functions, while positive SCP shifts ac- stantial training. This quality, combined with the relative ease of
company reduced cortical activation [98], [99]. Early studies acquisition of brain signals by EEG, makes a P300-based BCI
[100] confirmed the importance of the anterior brain regions potentially very practical for clinical use. Sellers et al. [19] and
in physiological regulation of SCP signals and suggested these Nijboer et al. [92] have reported that ALS patients are able to
areas are important for successful use of this type of BCI [73]. communicate using a P300 speller. Successful use of a P300
With extensive training, sometimes months [17], the user learns BCI has also been reported for people with disabilities resulting
to control SCP positive or negative voltage shifts. The BCI trans- from stroke, spinal-cord injury, cerebral palsy, multiple scle-
lates these voltage shifts into vertical movement of a cursor or rosis, and other disorders [115], [116]. In these systems, com-
an object on a computer screen. By this means, binary selec- munication can be greatly enhanced by appropriate software
tion or control can be achieved. Based on this principle, Bir- such as a text-to-speech synthesizer and a word-prediction pro-
baumer et al. developed an early BCI-controlled spelling device gram. A P300 BCI system based on auditory stimuli would be
[10], [101]. A series of studies in people with ALS and other useful for patients with limited or restricted eye movement or
severe neurological diseases in different stages of physical im- eyesight; such BCIs are currently under development [19], [21],
pairment confirmed the ability of the SCP BCI to provide basic [117], [118].
communication capability [102]–[104]. Despite these achieve-
ments, SCPs provide only very slow communication (e.g., one D. Movement Control
minute per letter [17]). Moreover, a comparative study [17] sug- Restoration of motor control in paralyzed patients is another
gested that, for people severely disabled by ALS, an SMR-based key application of BCI and is the main goal of many researchers
or P300-based BCI system is a better option than an SCP-based in the field. The research in this clinical application is sparse
BCI. and has used mainly SMR-based systems. Wolpaw et al. have
Sensorimotor rhythms, also recorded by EEG, have also demonstrated one-, two- [83], and even three-dimensional
proved to provide features suitable for BCI-enabled commu- cursor control using an SMR system [22] and have done pre-
nication and have been used successfully by several research liminary experiments with SMR control of a robotic arm [119].
groups [37], [83], [85]. Typically, the SMRs are recorded over These experiments indicate that SMR BCI systems might be
sensorimotor cortex and the features useful for BCI are the able to support multidimensional control of the movement of
rhythm (8–12 Hz) and the rhythm (18–26 Hz). Fig. 1(a) (i) motor neuroprosthesis or an orthotic device such as a robotic
illustrates a BCI based on SMRs. Changes in and rhythm arm. Pfurtscheller and colleagues tested an SMR-based BCI for
amplitudes are referred to as event-related desynchronization restoration of motor control in paralyzed patients (for review,
(ERD) (i.e., decrease) and event-related synchronization (ERS) see [37]). A tetraplegic patient was trained to control an elec-
(i.e., increase). Typically, changes in and rhythms are trically driven hand orthosis with EEG signals recorded over
associated with movement, sensation, and motor imagery. sensorimotor cortex [120]. By learning to generate separable
The rhythms decrease or desynchronize with movement or its motor imagery tasks, this patient was able to open and close his
preparation, and increase or synchronize after movement and paralyzed hand with the hand orthosis.
with relaxation [105]. However, people can learn to use motor Functional electrical stimulation (FES) can also be used for
imagery, rather than actual movement, to change SMR ampli- restoration of motor function in paralyzed patients with intact
tudes, and can use that control to operate a BCI. Work in several lower motor neuron and peripheral nerve function. With the goal
laboratories has shown that an SMR-based BCI can enable of further enhancing motor restoration in paralyzed patients,
basic word processing and icon selection [7], [12], [37], [83], Pfurtscheller and his colleagues combined the SMR BCI with
[85], [106]–[111]. These studies amply demonstrate that, with FES systems and tested the combined system in two patients
training, most people with or without motor disabilities can use with high-spinal-cord injury [67], [68].
SMR amplitudes to select targets by controlling the one-, two-,
or three-dimensional movements of a cursor [22], [83]. E. Environmental Control
The third major type of EEG-based BCI communication uses BCI-based environmental control could greatly improve the
the well-studied P300 even-related brain potential [5], [11] to quality of life of severely disabled people. People with severe
indicate the response to a salient or infrequent stimulus within motor disabilities are often home-bound. Effective means for
a stream of frequent standard stimuli. Fig. 1(a) (ii) illustrates a controlling their environments (e.g., controlling room tempera-
BCI based on P300. Detected in EEG recordings over the cen- ture, light, power beds, TV, etc.) would increase their well-being
tral and parietal regions, the P300 signal is a positive deflec- and sense of independence [88], [93], [121]. A recent pilot study
tion of brain wave at a latency of about 300 ms [112]–[114]. by Cincotti et al. [88] attempted to integrate BCI technology into
The stimuli used in most P300 BCI systems reported to date a domestic environmental control system. With unified control

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194 IEEE REVIEWS IN BIOMEDICAL ENGINEERING, VOL. 2, 2009

through EEG-based BCI technology, the user is able to operate idea that more normal activity will result in more normal CNS
remotely domestic devices such as neon lights and bulbs, TV function and will thereby improve motor control. Since prelim-
and stereo sets, a motorized bed, an acoustic alarm, a front door inary results in stroke patients demonstrate that they can gain
opener, and a telephone, as well as to monitor the surrounding control of specific brain activity patterns [50], [73], a BCI might
environment through wireless cameras. The clinical validation be used to enhance this control by measuring and extracting
of the system prototype took place in a simulated home environ- EEG features that can be translated into feedback to the user.
ment in an occupational therapy department. Fourteen healthy Daly et al. [127] measured EEG activity from stroke patients be-
normal subjects and four subjects suffering from spinal mus- fore and after this EEG-based neurorehabilition. After the motor
cular atrophy type II (SMA II) or Duchenne Muscular Dys- relearning intervention, EEG features were found to change in
trophy (DMD) were tested. The patients were able to control parallel with improvement in motor function. Moreover, a re-
the system with an average accuracy of 60–75% over the last cent study by Enzinger et al. [128] reported that sensorimotor
three testing session (8–12 sessions in total). Preliminary find- rehabilitation using BCI training and motor imagery improved
ings from this study suggested that the self-control of the do- motor function after CNS injury.
mestic environment realized with BCI technology increased the The second strategy for producing improved motor control
patient’s sense of independence. Also, caregivers could be re- is to use the output from a BCI to activate a device that assists
lieved to some extent from the need to be continually present. movement. This approach is based on the hypothesis that the
CNS plasticity induced by the sensory input produced during
F. Locomotion the improved motor function provided by the device will lead
Restoration of independent locomotion is another important to improved motor control. In past studies, neurorehabili-
issue for paralyzed people. In light of this, several BCI research tation training with robotic devices that assisted movement
groups have attempted to develop BCI-driven wheelchairs in has been effective in stroke patients [129]. Daly et al. have
order to restore some form of mobility. Tanaka et al. devel- done promising preliminary work combining BCI with FES or
oped an electric wheelchair controlled by EEG [122]. Direc- assistive robotics for motor relearning in stroke patients [130].
tional commands were detected by EEG and were then applied BCI-based therapy might provide a useful complement to
to direct control of the wheelchair. Such precise control may be standard neurorehabilitation methods and might lower cost by
quite demanding on the user. Rebsamen et al. reported a wheel- reducing the need for the constant presence of a rehabilitation
chair controlled by a P300-BCI system [123] in which the user therapist.
simply selects a destination from a menu of destinations. While
this approach is less demanding for the user, the capacity for IV. LIMITATIONS OF CURRENT BCIs
real-time directional control of the wheelchair is limited by the All of the BCIs currently under development have limitations.
selections, and prior definition of the possible paths is needed. Issues of safety and the long-term stability of the recording elec-
Millán and his group studied a BCI-controlled wheelchair that is trodes used in invasive BCI systems remain to be resolved sat-
based on the EEG activity associated with various mental tasks isfactorily. Some, but not all, of these concerns may be resolved
and a shared control system [86], [124]. It employed intelligent when it becomes possible to fully implant a telemetric device to
algorithms to assist the user in obtaining continuous command transmit the recorded brain signals. Nevertheless, the electrodes
of the system during wheelchair navigation. Further work is re- can be implanted in only a relatively small number of areas and
quired to confirm the usability of a BCI-driven wheelchair in the can record from relatively limited populations of cells. In con-
real-world environment. For this application, due to considera- trast, EEG-based BCI systems, which are noninvasive and do
tions of safety, there must be stricter requirements for accuracy not require surgery or the long-term maintenance of implanted
than for many other BCI applications. electrodes, do not have the risks of surgery or the questions of
long-term stability of the electrodes since the electrodes are ex-
G. Neurorehabilitation ternal and easily replaced. On the other hand, the brain sig-
In addition to their uses for communication and control, BCI nals detected by EEG-based systems are relatively weak and
systems also have potential to serve as therapeutic tools to help of limited frequency range. Nevertheless, EEG-based BCIs are
people whose neuromuscular function has been impaired by currently adaptable for practical independent use by disabled
trauma or disease to relearn useful motor function. Neurore- people outside of the laboratory [131] and are in fact currently in
habilitation using BCI systems promotes functional recovery use by a small number of paralyzed people at home in their daily
and may improve quality of life [95]. This specific application lives [33]. Despite this achievement, continuing development
of BCI systems seeks to augment current rehabilitation thera- of practical EEG-based BCI systems is needed to address ex-
pies by reinforcing and thereby increasing effective use of im- isting issues. The extent of available independent control chan-
paired brain areas and connections [125], [126]. This approach nels in such recordings remains to be determined. Continued de-
to rehabilitation was first evaluated with MEG signals in people velopment of noninvasive BCI systems with multiple indepen-
with strokes and found cortical reorganization after BCI-based dent control channels could substantially expand the capacity
training [50]. of BCI applications (e.g., multidimensional control of neuro-
In a recent review, Daly and Wolpaw [29] classified the pos- prosthesis).
sible BCI-based motor learning strategies into two categories. Another possible obstacle to moving BCI technology into
In the first, patients are trained to produce more normal brain practical use is their demand on the user’s attention. Rapid
activity to control motor function. This strategy is based on the fatigue of users has been previously reported in certain studies

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MAK AND WOLPAW: CLINICAL APPLICATIONS OF BRAIN–COMPUTER INTERFACES 195

of BCI control [49], [123], and inconsistent performance by erature to date concerns development of improved signal pro-
individual users is characteristic of most methods. Ongoing cessing or other engineering facets of BCI technology, incorpo-
changes in the user’s performance (due to fatigue, distraction, ration of professionals from all the above mentioned disciplines
disease progression, etc.) require continuing adaptation of is critical for success [135].
the BCI system. Some BCI applications currently require an As a field of practice and a subject of study, BCI technology
exhaustive series of user commands (e.g., different mental is still in its infancy. Further research on different components
activation tasks); these might be reduced by development of of BCI development is ongoing and challenging. These include
intelligent adaptation and learning algorithms. Further ad- explorations of useful brain signals; signal recording tech-
vances in other areas, such as speed, accuracy, consistency, niques; feature extraction and translation methods; methods for
convenience, and cosmesis, are also important for successful engaging short- and long-term adaptations between user and
implementation of practical BCI systems. system so as to optimize performance; appropriate BCI appli-
cations; and clinical validation, dissemination, and support.
V. PROBLEMS OF DISSEMINATION AND SUPPORT Efforts have recently begun to translate laboratory-validated
All current BCIs require significant efforts to set up, cali- BCI technologies into home systems for severely disabled in-
brate, and operate [1]. The kind and degree of effort vary sub- dividuals [33]. These home systems are currently limited to
stantially across BCIs. LFP-, spike-, or ECoG-driven BCIs re- applications for simple communication (e.g., word processing,
quire surgery and constant monitoring of the scalp-port through speech synthesizing, and e-mail, etc.) and simple environmental
which the wires run to the electrodes. EEG electrodes, which control (e.g., TV, room temperature, etc.) Widespread dissemi-
can be applied in a few minutes, require periodic reapplications. nation of these BCI systems may be difficult, since the fact that
Daily recalibration may be needed (particularly for intracortical the limited capacities of current BCIs make them useful to only
BCIs). A number of key issues have to be addressed in order relatively small populations of users means that they are un-
to transfer BCI technology from the laboratory to clinical set- likely to attract significant commercial interest. In response to
ting [30]. These include the ease and convenience of daily use, this problem, a new noncommercial option for BCI dissemina-
cosmesis, safety, reliability, usefulness of the BCI applications tion has recently been initiated.1 Other BCI applications, such
in the user’s daily life, and the need for ongoing expert tech- as restoration of motor function, have been confined mainly to
nical oversight. The cost of ongoing technical support may be laboratory settings or limited lab-based demonstrations and are
high, and such support may only be available from a few re- not yet being used in everyday life [17]. Further work in all
search groups. Therefore, the development of standardized BCI these areas is needed for BCIs to be validated and shown to be
systems with reduced complexity and minimal need for ongoing practical for the real-life environments of home-bound users.
technical support is essential for the widespread dissemination The use of BCI applications in neurorehabilitation is another
of BCI technology. promising area that is as yet still in its infancy.
The physical and social circumstances of potential BCI users,
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MAK AND WOLPAW: CLINICAL APPLICATIONS OF BRAIN–COMPUTER INTERFACES 199

Joseph N. Mak (S’07–M’08) received the Ph.D. Jonathan R. Wolpaw received the M.D. degree from
degree in biomedical engineering from the Univer- Case Western Reserve University, Cleveland, OH.
sity of Hong Kong, China, in 2009. He is currently He is Chief of the Laboratory of Neural Injury
a Postdoctoral research fellow at the Laboratory of and Repair at the Wadsworth Center of the New
Neural Injury and Repair, Division of Translational York State Department of Health and a Professor of
Medicine, Wadsworth Center, New York State Biomedical Sciences at the State University of New
Department of Health, Albany, NY. York (SUNY), Albany. His laboratory has developed
His main research interests includes brain–com- and is using operant conditioning of spinal reflexes
puter interfaces, system neuroscience, neural and re- to define the plasticity underlying learning and as
habilitation engineering. a new therapeutic approach to improve walking
after spinal cord injury. He is also leading the
development of EEG-based brain–computer interface (BCI) technology to
restore communication and control to people who are paralyzed. His group
has shown that non-invasive EEG-based BCI technology can give control
similar to that achieved by electrodes placed in the brain, and has begun to
provide BCI systems to severely disabled people for daily use in their homes.
These achievements have received wide recognition and numerous national
and international awards.
Dr. Wolpaw is a member of the American Neurological Association, the
American Academy of Neurology, the American Electroencephalographic
Society, and the New York Academy of Sciences Society for Neuroscience.

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