SPECIAL INTEREST ARTICLES
Applications of Electroencephalography to Characterize
Brain Activity: Perspectives in Stroke
Michael R. Borich, DPT, PhD, Katlyn E. Brown, MSc, Bimal Lakhani, PhD, and Lara A. Boyd, PT, PhD
A wide array of neuroimaging technologies are now available that
offer unprecedented opportunities to study the brain in health and
disease. Each technology has associated strengths and weaknesses
that need to be considered to maximize their utility, especially when
used in combination. One imaging technology, electroencephalogra-
phy (EEG), has been in use for more than 80 years, but as a result of
recent technologic advancements EEG has received renewed interest
as an inexpensive, noninvasive and versatile technique to evaluate
neural activity in the brain. In part, this is due to new opportunities to
combine EEG not only with other imaging modalities, but also with
neurostimulation and robotics technologies. When used in combina-
tion, noninvasive brain stimulation and EEG can be used to study
cause-and-effect relationships between interconnected brain regions
providing new avenues to study brain function. Although many of
these approaches are still in the developmental phase, there is sub-
stantial promise in their ability to deepen our understanding of brain
function. The ability to capture the causal relationships between brain
function and behavior in individuals with neurologic disorders or in-
jury has important clinical implications for the development of novel
biomarkers of recovery and response to therapeutic interventions. The
goals of this paper are to provide an overview of the fundamental prin-
ciples of EEG; discuss past, present, and future applications of EEG
in the clinical management of stroke; and introduce the technique
of combining EEG with a form of noninvasive brain stimulation,
Division of Physical Therapy, Department of Rehabilitation Medicine, Emory
University School of Medicine, Atlanta, GA (M.R.B.); and Department
of Physical Therapy, Faculty of Medicine (K.E.B., B.L., L.A.B.), and
Centre for Brain Health, Faculty of Medicine (L.A.B.), University of British
Columbia, Vancouver, British Columbia, Canada.
M.R.B. was supported in part by a postdoctoral research fellowship from
the Heart and Stroke Foundation of Canada. K.E.B. was supported by the
Natural Sciences and Engineering Research Council of Canada. B.L. is
supported by the Heart and Stroke Foundation of Canada and the Michael
Smith Foundation for Health Research (MSFHR). L.A.B. receives salary
support from the Canada Research Chairs and the MSFHR.
At the time of submission, the work represented in the manuscript has not
been represented at any scientific meeting or in published form.
The authors have no significant conflicts of interest to disclose.
Supplemental digital content is available for this article. Direct URL citation
appears in the printed text and is provided in the HTML and PDF versions
of this article on the journal’s Web site (www.jnpt.org).
Correspondence: Michael R. Borich, DPT, PhD, Division of Physical
Therapy, Department of Rehabilitation Medicine, Emory University
School of Medicine, 1441 Clifton Rd NE, R228, Atlanta, GA 30322
(michael.borich@emory.edu).
Copyright C 2015 Neurology Section, APTA.
ISSN: 1557-0576/15/3901-0043
DOI: 10.1097/NPT.0000000000000072
JNPT r Volume 39, January 2015
Copyright © 2015 Neurology Section, APTA. Unauthorized reproduction of this article is prohibited.
transcranial magnetic stimulation, as a powerful synergistic research
paradigm to characterize brain function in both health and disease.
Video Abstract available (see Supplemental Digital Content 1, http:
//links.lww.com/JNPT/A87) for more insights from the authors.
Key words: electroencephalography, neuroimaging, rehabilitation,
stroke, transcranial magnetic stimulation, TMS-EEG
(JNPT 2015;39: 43–51)
INTRODUCTION
T here are now a number of ways to create a window into
the structure and function of the human nervous system.
Computed tomography (CT) and magnetic resonance imaging
(MRI) can identify fine structural abnormalities in the brain
and are used routinely in medical practice. However, there
are a number of contraindications to CT scanning and MRI,
and both are costly to administer. Other imaging approaches
(positron emission tomography and magnetic resonance spec-
troscopy) can detect changes in brain metabolism or metabolite
concentrations. Radiation exposure and cost are 2 limitations
of positron emission tomography, and the use of magnetic
resonance spectroscopy faces the same contraindications as
MRI. Functional brain imaging approaches, such as func-
tional (f)MRI and magenetoencephalography, are also costly
and technically challenging, whereas functional near-infrared
spectroscopy is less costly and more clinically feasible than
other approaches; however, it offers an indirect measure of
brain activity.
Electroencephalography (EEG) is a low-cost, noninva-
sive imaging technique that measures neuroelectric activity
in the brain with excellent temporal resolution. Electroen-
cephalograph has almost no contraindications, making it an
attractive approach for clinical populations. In the following
sections, we introduce the basic principles of EEG before high-
lighting clinical applications of EEG, using stroke as an exam-
ple. Then, we present a recently developed paradigm to study
brain function using simultaneous EEG recording with a form
of noninvasive brain stimulation, transcranial magnetic stim-
ulation (TMS). We conclude by discussing the potential bene-
fits of combining EEG with TMS and highlight other emerg-
ing EEG-related rehabilitation technologies that can improve
our understanding of brain function in neurologic clinical
populations that can leveraged into improving rehabilitation
outcomes.
43
Borich et al
A BRIEF HISTORY OF EEG
Berger1 initially collected the first EEG recordings in
human subjects in 1924. This work utilized 3 surface elec-
trodes placed on the scalp to noninvasively document rhyth-
mic oscillations in electrical potentials.2 These potentials are
generated from a mixture of synchronous excitatory and in-
hibitory postsynaptic currents in similarly oriented neuronal
cell populations.3,4 In the intervening 90 years, there have been
major technological advances improving the quality of EEG
recordings; expanded electrode configurations now allow for
quantification of neural activity from various brain regions and
analysis of neural networks, and computational advances now
enable the processing and storage of large data sets. Further-
more, EEG can be combined with other imaging approaches
to increase the amount and type of available data for analysis.
For example, combining EEG and MRI offers the excellent
temporal resolution provided by EEG with the high spatial
resolution of MRI.
Since its inception, EEG has been used in a myriad of
research applications to measure specific aspects of brain activ-
ity. Electrical oscillations, a fundamental organizing property
of brain activity,3 and responses to environmental stimuli can
be examined at rest and during behavior. Electroencephalog-
raphy has been used to investigate cognitive processes un-
derlying perception,5 decision making,6 and action.7 Clini-
cally, EEG measures can inform the diagnosis, prognosis, and
treatment response for many disorders including epilepsy,8
schizophrenia,9 altered consciousness,10 sleep,11 tumors,12
traumatic brain injury,13 and stroke.14
BASIC EEG METHODOLOGY
Data Acquisition
Electroencephalography utilizes noninvasive electrodes
covering the scalp to quantify neuroelectric currents in the
brain. Electric potentials detected by scalp electrodes depend
both on the strength of the electric field resulting from local
field potentials summed within populations of thousands of
neurons, biological properties of the conducting media, and
distance between the current generators and scalp.3 Capturing
electrical activity through an external electrode exploits the
principles of the Ohm’s Law—current measured through a con-
ductor is dependent on the voltage applied and the impedance
or resistance.3 Current simply refers to the flow of an electric
charge, whereas impedance reflects the degree of hindrance
to the time-varying flow of current. Therefore, minimizing ex-
ogenous sources of impedance (hair, skin cells, oils, etc) during
electrode preparation is important. To ensure controlled and
reproducible scalp recordings, an electrode (Cz) is commonly
placed over the center of the head (vertex). Electrode arrange-
ments, known as montages, are highly customizable based
on the population studied, information desired, and record-
ing conditions (Figure 1). Although full montage preparation
is typical, EEG setups containing only a ground electrode, a
reference electrode, and a single active electrode can be used.
Conversely, EEG recordings can be made from montages up to
256 electrodes, greatly increasing the amount of information
available for analysis.
44
Copyright © 2015 Neurology Section, APTA. Unauthorized reproduction of this article is prohibited.
JNPT r Volume 39, January 2015
Figure 1. A 28-channel custom electrode montage for
recording scalp-based activity over primarily centrally located
cortical regions. Cz (vertex) is located at the center of the
head.
Data Analysis
Electroencephalography recordings can be studied us-
ing various approaches that depend on the research or clin-
ical question of interest and the experimental testing con-
ditions employed. There are 2 primary EEG experimental
paradigms—the event-related potential (ERP) technique and
the continuous recording of ongoing brain activity. Event-
related potentials are the result of specific cortical activation
patterns associated with a specific event.15 These events can
be external sensory stimulations such as a vibratory stimulus
applied to the finger or can be internal such as the onset of
a movement. Early ERP components are largely seen in pri-
mary processing regions and reflect the arrival of information
in the area covered by the electrode, whereas the later compo-
nents are thought to reflect higher-order processing occurring
primarily in secondary cortical areas or association areas.16
Electroencephalography can also monitor and quantify spon-
taneous oscillatory activity when recorded continuously. This
approach is commonly used to evaluate patterns of brain ac-
tivity during different arousal states (eg, altered consciousness
or sleep) or in response to interventions over time.3,17
Multiple frequency bands associated with cortical func-
tioning have been documented (Table 1). Delta waves (0.5-4
Hz), theta waves (4-7 Hz), and alpha waves (8-13 Hz) are con-
sidered to be indicators of widespread cortical processing.18
These waves are seen across numerous cortical regions and
relate to the integration of activity among brain regions. Mod-
ulations in frequency band amplitude are thought to be indica-
tive of patterns of cortical activation and deactivation, such
that regions showing related frequency changes likely repre-
sent an information-processing network underlying behavior.4
Alterations in frequency band amplitude may be associated
with event-related changes; however, they are not noted until
hundreds of milliseconds after a stimulus, suggesting that they

C 2015 Neurology Section, APTA
JNPT r Volume 39, January 2015 Applications of Electroencephalography to Characterize Brain Activity

provide a clearer measure of sustained task-related changes
in activation patterns, rather than immediate responses to
stimuli.19
Frequency oscillations can be examined in continuous
data to determine the state of cortical activity at rest, or they
can be documented in relation to a specific event. Phase syn-
chronization of such oscillations may be examined in the
following 3 ways: (1) phase coupling over distance, (2)
phase coupling between frequencies, or (3) phase lock-
ing due to an external stimulus. Each measure provides
unique information on frequency rhythms at immediate time
points.36
Coherence examines whether shifts in oscillations in
separate cortical areas are correlated with one another.
Evidence of phase coupling between distant brain regions
likely suggests an interconnected neural network.36 For ex-
ample, coherence may provide a useful method to investigate
changes in the motor preparation network, as opposed to sim-
ply quantifying local motor cortex excitability.
Phase coupling can also occur between oscillations of
differing frequencies. Functionally, this phenomenon may be
important for communication between separate, yet interre-
lated networks.37 Communication between 2 such networks is
inferred from a constant phase lag between oscillations mea-
sured at a specific time point.37–39 If communication between
networks is expected to be altered following a treatment, phase
coupling could address this question.
Phase locking can also occur when recording ERPs.
Event-related potentials may result from phase resetting of
brain oscillations.40,41 Therefore, ERPs provide an immediate
glimpse into the effect of peripheral stimuli on underlying brain
activity. Event-related potentials are typically modality spe-
cific; for example, somatosensory-evoked potentials (SEPs)
are elicited by peripheral nerve stimulation and represent af-
ferent information processing in the contralateral sensorimo-
tor cortex (Figure 2). This brief overview of common data
acquisition and analysis approaches highlights the versatility
of EEG and demonstrates the importance of closely aligning
EEG recording parameters to the specific clinical or research
question to be addressed.
PROS AND CONS OF EEG TO MEASURE
CHANGES IN BRAIN ACTIVITY
Although EEG has a number of strengths that make it
an attractive imaging technology, traditional EEG has a num-
ber of potential pitfalls that need to be considered. The chief
limitation of EEG is low spatial resolution. Electrode loca-
tions provide gross localization for the distribution of cortical
activity, and spatial accuracy can potentially be improved by

Table 1. Major Oscillatory Frequency Bands Observed in EEG Recording With Associated Source of Activity and
Relationship to Cognitive Processing
Frequency Band Current Generator Role in Processing
Delta (0-4 Hz) Thalamocortical/neocortical20 Cortical integration21
Attention22
Language processes22−24
Theta (4-7 Hz) Cortical/hippocampal25 Virtual navigation25
Declarative memory26
Episodic memory27,28
Alpha (8-13 Hz) Thalamocortical29 Cortical/behavioral deactivation or inhibition30,31
Beta (13-30 Hz) Cortical32 Motor function/voluntary movement33
Attention/executive functioning34
Gamma (30-80 Hz) Neocortical20 Encoding, retention, retrieval of sensory information (for review35 )

Figure 2. An example of a representative somatosensory-evoked potential (SEP) collected from a young, healthy individual. The
primary peaks in the waveform are labeled. N20 is thought to represent the arrival of afferent information to the contralateral
somatosensory cortex. P100 is associated with bilateral secondary somatosensory cortical processing of the afferent information.
The P300 represents attentional, context-based sensory processing in the parietal and cingulate cortices. Long-latency
potentials, also thought to be associated with processing of sensory information, are shown between 100 ms and 300 ms.


C 2015 Neurology Section, APTA 45

Copyright © 2015 Neurology Section, APTA. Unauthorized reproduction of this article is prohibited.
Borich et al JNPT r Volume 39, January 2015

increasing the number of recording electrodes42,43 ; however,
true 3-dimenstional spatial localization with EEG is not pos-
sible, an important consideration for brains that have reorga-
nized as a result of lesions or damage. Pairing EEG techniques
with MRI, which has high spatial resolution (mm) can, in part,
mitigate this limitation.44
Another challenge of EEG technology is that the strength
of the signal dissipates with distance from current-generating
sources and is influenced by tissue characteristics within the
brain. Source estimation on the basis of the scalp potentials
is imperfect; activity of a single source can be represented
across many electrodes. Therefore, scalp signals are not equal
to source signals. This situation is akin to the cocktail party
analogy, where a microphone placed in a room will pick up
sound from a mixture of sources, making difficult to interpret
the precise location of individual sources of sound. Similarly,
a single electrode on the scalp will pick up activity from a
multitude of sources (cortical electrical activity, subcortical
activity, external noise, etc), leading to difficulty in accurately
localizing the source of activity. Multiple algorithms and com-
putational approaches have now been developed that can im-
prove source localization.45−47 Recognizing that there are an
infinite number of current-generating dipoles within the brain
that could explain the voltages measured on the scalp by EEG
is important.42 As a result, localizing observed EEG activity
to the actual current-generating source within the brain with
absolute certainty is impossible.
Finally, EEG may be influenced by external factors such
as participant alertness and environmental noise. Monitoring
and maintaining a desired arousal level and eliminating as
many unwanted sources of electrical noise as possible during
recording become critical. Capitalizing on the strengths and
minimizing the weaknesses of EEG are important considera-
tions of this technology in both research and clinical applica-
tions. The following section discusses the utility of EEG in
characterizing brain behavior after stroke as an example.
USING EEG TO MEASURE BRAIN ACTIVITY
AFTER STROKE
Functional impairments following stroke are a result of
direct ischemic loss of neurons combined with maladaptive
brain reorganization.48 Measuring these changes in brain or-
ganization and activity has become possible through advances
in neuroimaging and neurostimulation techniques. Yet, there
is still a limited understanding of the relationships between
reorganization of individual brain regions with one other
and within coherent networks of functional brain activity.
For decades, EEG has been used as a prognostic, diagnos-
tic, and therapeutic tool during stroke recovery49 (Table 2).
Somatosensory-evoked potentials are frequently measured
acutely as a means to assess cortical responses to external
perturbations to predict motor recovery following stroke.50,51
Abnormal SEPs also correlate with increased length of acute
rehabilitation stay52 and poorer functional outcomes.50,52
However, while SEPs alone may have limited prognostic util-
ity for determining long-term functional outcomes after stroke,
the combination of EEG measures with motor-evoked poten-
tials (MEPs) using noninvasive brain stimulation53 and clinical
variables50 may improve predictive accuracy after stroke.
During stroke rehabilitation, the focus is often on suc-
cessful performance of functional motor tasks to demonstrate
recovery progress. Electroencephalography can be used to
parse the potential deficits involved within individual pro-
cessing stages of producing voluntary movement (ie, motor
planning vs movement completion). For example, the contin-
gent negative variation (CNV), a slow-wave ERP beginning
approximately 2 seconds prior to a predictable cued stimulus,
reveals cognitive preparation and planning prior to action.67,68
In healthy individuals, the CNV is primarily observed con-
tralateral to the side of movement (ie, in the active hemisphere).
Whereas individuals with chronic stroke with lesser functional
recovery display a midline shift in the CNV during cued move-
ment preparation compared with the nonparetic hand.61 This
shift is thought to be associated with maladaptive reorgani-
zation after stroke.61 However, despite poor motor recovery,
the neural mechanisms that underlie movement preparation of
the paretic limb are maintained albeit reorganized. Therefore,
rehabilitation interventions focusing on the preparatory phase
of movement generation may encourage positive functional
reorganization to support paretic extremity function.
Longitudinal EEG recording may be of value in as-
sessing and predicting recovery trajectories. Impairments

Table 2. Utility of Common EEG Measures in Stroke Recovery and Rehabilitation

Utility EEG Measure Outcomes
Prognostic Somatosensory-evoked potentials (SEPs) Correlated with length of inpatient stay52
Predictor of long-term functional recovery50,52
Spectral analysis Improved mean power spectrum did not relate to clinical outcomes at 3 or 6 mo poststroke54
Quantitative (q)EEG Identifies individuals with poor prognosis for functional recovery55
Alpha and theta frequency band power predict short-term functional outcomes56
Significant correlation with residual functional disability14
Brain symmetry index positively correlated with disability levels at 6 mo57
Diagnostic Synchronization Increased desynchronization in beta band activity during movement58
Asynchrony in beta and gamma bands during movement planning and execution59
Reduced interhemispheric synchrony following stroke60
Therapeutic Contingent negative variation (CNV) Cueing paretic limb movement shifts CNV to midline61
Brain-computer interfaces (BCIs) Allows manipulation of upper-extremity orthoses during imagined movement of the paretic limb62–65
Event-related desynchronization triggers FES activation of a target muscle66
Abbreviations: BCI, brain-computer interfaces; CNV, contingent negative variation; EEG, electroencephalography; FES, functional electric stimulation; (q)EEG, quantitative EEG;
SEPs, somatosensory-evoked potentials.

46 
C 2015 Neurology Section, APTA

Copyright © 2015 Neurology Section, APTA. Unauthorized reproduction of this article is prohibited.
JNPT r Volume 39, January 2015
following stroke are multifaceted, and efficacy of rehabilita-
tion is highly variable between individuals. The specific char-
acteristics contributing to individual therapeutic response re-
main incompletely understood. Advances in the quantitative
EEG (qEEG) analysis have resulted in an influx of promis-
ing results using qEEG as a prognostic marker of recovery
in stroke. Specifically, qEEG overcomes the problem of inter-
observer variability by objectively quantifying EEG features
using power spectrum analysis of frequency band content and
by computational modeling.69,70 Although early EEG studies
in individuals with stroke did not yield promising prognostic
results, qEEG variables recorded that immediately following
stroke were significantly correlated with residual disability
and showed greater prognostic accuracy than the Canadian
Neurological Scale Clinical stroke scale.14 More recent work
demonstrated that following ischemic stroke, alpha and theta
frequencies band power were significant predictors of short-
term functional outcomes, whereas delta absolute power was
a strong predictor of long-term functional outcomes.56 During
the subacute phase of stroke recovery, qEEG measures were
positively correlated with disability level (modified Rankin
scale values) at 6 months poststroke57 and could identify in-
dividuals with a poor prognosis for functional recovery.55 A
recent review concluded that qEEG is a sensitive approach
to detect interhemispheric asymmetries and can inform clin-
ical prognosis when collected during the subacute and acute
phases following ischemic stroke.71 The assessment of qEEG
within 72 hours of stroke diagnosis appears to be a useful
tool to predict short- and long-term functional outcomes af-
ter stroke.71 The clinical utility of qEEG to denote poststroke
markers of recovery will largely depend on the ability to im-
plement recordings into routine clinical care. Recent work has
shown that qEEG measures collected using a reduced electrode
montage (4 electrodes vs 19 electrodes) were correlated with
cognitive outcomes at 3 months poststroke.72 Although it may
not always outperform clinical assessments or imaging data,
EEG may be considered a potentially complementary measure
to routine clinic management.
Following stroke, the regional connectivity of brain re-
gions is also altered. Electroencephalography has been used to
measure time-dependent functional brain connectivity. Gerloff
et al73 demonstrated that following stroke cortico-cortical
connectivity was reduced in the ipsilesional hemisphere and
slightly increased in the contralesional hemisphere. Basic cor-
ticospinal commands are likely maintained by the ipsilesional
cortex, whereas higher-order corticospinal commands, such
as response selection and movement preparation, are medi-
ated by the contralesional hemisphere.73 Computational EEG
data modeling also suggest that there are connectivity dif-
ferences in persons with stroke compared with neurologi-
cally healthy persons during anticipation and execution of
self-initiated movements.59 Electroencephalography technol-
ogy has advanced the understanding of the temporal aspects of
cortical network connectivity following stroke that has clinical
implications; however, localization of these changes to specific
brain regions remains limited when EEG recordings are made
in isolation.
In addition to using EEG to identify neural biomarkers
of recovery after stroke, information from EEG can be

C 2015 Neurology Section, APTA
Copyright © 2015 Neurology Section, APTA. Unauthorized reproduction of this article is prohibited.
Applications of Electroencephalography to Characterize Brain Activity
harnessed for rehabilitation applications. Brain-computer
interfaces (BCIs) are being used to augment recovery for
individuals who typically demonstrate limited response
to therapeutic interventions following stroke65 and spinal
cord injury.74 Brain-computer interfaces allow individuals
with limited motor ability to manipulate an upper-extremity
orthosis by monitoring and quantifying EEG patterns in the
ipsilesional hemisphere during imagined movements of the
stroke-affected limb.62−65 Electroencephalography-driven
robotics can supplement motor function following stroke
with functional electric stimulation (FES). Functional electric
stimulation utilizes focal activation of target muscle during the
motor intention phase of movement using electromyography
from the effector itself.66 In cases where sufficient elec-
tromyography activity is not present, EEG activity associated
with movement intention can drive FES protocols.75 Although
BCI technologies are still primarily in the development
stage, the potential benefits for neurorehabilitation to address
impairments after stroke and other neurological disorders
present an important clinical application of EEG recording.
In an effort to further maximize the utility of EEG, novel
multimodal imaging approaches have been proposed that
offer promise in their ability to identify new biomarkers of
altered brain function and also recovery of function.
COMBINING EEG WITH TRANSCRANIAL
MAGNETIC STIMULATION
A promising synergistic approach to characterize brain
behavior is to combine EEG with TMS, a safe, noninvasive
method used to stimulate cortical regions to measure levels of
excitability. Transcranial magnetic stimulation essentially uti-
lizes a magnetic field to readily carry electrical current through
the skull painlessly and without current loss. When the coil
is positioned on the scalp, the magnetic field induces small
electrical currents in the underlying cortical tissue that can
depolarize neurons transynaptically.76 When positioned over
the primary motor cortex (M1), TMS can elicit a contralateral
peripheral muscle response (a MEP). These MEPs provide
information about excitability and integrity of corticospinal
pathways. Using this methodology, ipsilesional M1 excitabil-
ity is typically decreased following stroke,77,78 whereas con-
tralesional M1 excitability remains largely unchanged.79,80 Im-
portantly, this interhemispheric imbalance may interfere with
recovery.81,82
Recent technologic advances now offer the capacity to
combine TMS with EEG, to capitalize on the excellent tempo-
ral resolution and repeatability of EEG, in healthy individuals
and clinical populations.83–85 Real-time integration of TMS
and EEG provides the opportunity to directly characterize lo-
cal and distributed cortical activity to empirically determine
causal mechanisms of brain behavior in humans in vivo. This
approach also provides the opportunity to stimulate any brain
region and record the evoked activity using EEG, thus remov-
ing the need to elicit peripheral responses and infer cortical
activity (Figure 3). Therefore, it is now possible to study brain
behavior using TMS-elicited responses via EEG in any par-
ticipant even when there is extensive damage to descending
pathways. This ability could have important applications in
47
Borich et al JNPT r Volume 39, January 2015

Figure 3. Scalp electrode array depicting individual channel responses to transcranial magnetic stimulation (TMS) applied over
the left prefrontal cortex. The “X” denotes the scalp location of TMS delivery. Note the large evoked potential amplitudes in
neighboring channels and reduced, but present, responses in distant channels located near the right occipital and parietal
cortices. This illustrates the capacity for simultaneous TMS-EEG to perturb both local and remote cortical activity to evaluate
regional cortical excitability and connectivity. The y-axis has been scaled in each trace to enhance visualization of the small
amplitude responses evoked distant to the site of stimulation.

individuals with severely disrupted sensorimotor input/output
pathways. In persons with stroke, it can be difficult in many
cases to generate measurable MEPs from ipsilesional M1 when
the infarct location encroaches substantially on the descending
corticospinal tract.86 It has previously been shown in individ-
uals with chronic stoke where MEPs cannot be elicited from
the ipsilesional M1, recovery is less complete and response to
motor skill training is diminished.86 The ability to character-
ize brain behavior in this subset of persons with stroke using
TMS-EEG may offer insights that could inform rehabilitation
approaches for those with severe impairments after stroke.
The first successful report of TMS-evoked responses or
potentials (TEPs) captured by EEG was in 1997.87 Since that
time, significant technological advances now allow character-
ization of TEPs within 5 ms of stimulus delivery. Multiple re-
ports have demonstrated a characteristic TEP waveform either
recorded at the vertex (Cz) (Figure 4) or from the mean activ-
ity across electrodes. The characteristic positive and negative
deflections observed in EEG recordings have been shown to be
associated with brain activity in both cortical and subcortical
regions in neurologically healthy individuals.42 Importantly,
TEPs have been shown to be highly reproducible demonstrat-
ing excellent test-retest reliability in healthy participants.83 A
TMS pulse can directly activate an area of cortical tissue ap-
proximately 1 cm2 at a depth of ∼1 to 2 cm depending on
stimulation intensity. Thus, TEPs observed beyond local re-
gion of stimulation can be used to evaluate the spatiotemporal
dynamics of intra-88 and interhemispheric89 connectivity as a
result of activation a specific cortical region. This approach
could be used to directly evaluate the status of specific neural
pathways thought to play an important role in functional recov-
ery following stroke. However, local cortical excitability and
cortico-cortical connectivity have yet to be characterized using
simultaneous TMS-EEG in participants with chronic stroke.
Using real-time TMS-EEG, one can understand differ-
ences in brain excitability and connectivity in the context of
neurologic injury and/or disease and also evaluate changes in
brain behavior in response to interventions (pharmacological,
behavioral, and stimulation) or associated with spontaneous
recovery. These 2 approaches can also be combined in an
“off-line” design to circumvent the technological challenges
of recording small amplitude EEG signals in the harsh TMS
environment (for review, see Siebner et al43 ).
There are many challenges associated with combined
TMS-EEG. Transcranial magnetic stimulation–evoked neu-
roelectric activity is susceptible to multiple artifact sources
including the large electrical field induced by coil dis-
charge, muscle activation near the stimulation site, auditory-
evoked potentials, eye blink artifacts, and artifacts associ-
ated with recharging the TMS capacitor. Because of current

48 
C 2015 Neurology Section, APTA

Copyright © 2015 Neurology Section, APTA. Unauthorized reproduction of this article is prohibited.
JNPT r Volume 39, January 2015 Applications of Electroencephalography to Characterize Brain Activity

Figure 4. An example of TMS-evoked potentials (TEPs) recorded from the vertex (Cz) during TMS applied over the left primary
motor cortex. Characteristic deflections in the waveform are labeled (P30, N45, P60, N100, and P180). Note the large
stimulation artifact beginning around 0 ms that is resolved by approximately 10 ms following stimulation. The rapid return of
EEG activity toward baseline levels after TMS delivery allows for the visualization of early, smaller amplitude peaks generated
from evoked cortical activity to characterize immediate cortical responses to TMS.

methodological challenges and the cost of TMS stimulators,
TMS-EEG will probably not soon become a part of routine
clinical practice. Despite these challenges, combining these
methodologies allows highly specific and repeatable perturba-
tions to any cortical region using TMS and can be used in re-
search investigations to evaluate (1) local cortical excitability,
(2) spread of induced activation in time and space, (3) con-
duction times between the stimulated region and other cortical
regions, and (4) changes in complex brain dynamics such as
frequency band power or coherence using EEG. Furthermore,
TMS-EEG can be used to evaluate the casual neural mech-
anisms underlying behavior. The ability to characterize the
salient neural substrates of behavior may have important clini-
cal implications for the design, delivery, and individualization
of therapeutic interventions for individuals with neurologic
conditions.
IMPLICATIONS FOR CLINICAL PRACTICE AND
FUTURE DIRECTIONS
The capacity of EEG to measure electrical activity of the
brain generated by postsynaptic potentials in neuronal popu-
lations continues to offer a powerful noninvasive, low-cost,
widely applicable technique to study human brain behavior
in a myriad of research paradigms and clinical populations.
When combined with TMS, EEG has the potential to reveal
causal mechanisms of altered cortical excitability and connec-
tivity in neurologic disorders including stroke. It is inviting to
speculate that an improved mechanistic understanding of the
salient neural substrates underlying functional impairments
and activity limitations observed in persons with neurological
disorders will lead to new opportunities to develop targeted
clinical interventions to restore previous levels of function.
Using TMS-EEG to identify unique signatures of disordered
cortical connectivity associated with certain stroke subtypes
could inform clinical decision-making algorithms and foster
the personalization of rehabilitation interventions. For exam-
ple, distinct connectivity patterns consistent with a particular
stroke subtype could be a negative prognostic indicator for re-
sponse to a standard clinical intervention and may suggest an
alternative treatment option (eg, noninvasive brain stimulation
and pharmacological intervention). Improved characterization
of altered brain behavior after stroke to provide better prog-
nostic information demonstrates 1 potential future clinical ap-
plication for EEG to aid in treatment selection and improved
allocation of rehabilitation resources.
Combining EEG with BCI strategies offers additional
avenues to support the recovery of motor function for individ-
uals with severe motor impairments in situations where motor
output pathways may no longer be intact.90,91 As a result, it
could be possible to restore effective command of movement
by using EEG-based signal detection of motor cortical network
activity to bypass pathways that have been irreversibly dam-
aged. This example demonstrates the potential clinical utility
of EEG to noninvasively control a neuroprosthesis to perform
movements in persons for whom independent motor control is
not possible.
SUMMARY
In summary, recent novel technological developments
and sophisticated multimodal research approaches have cre-
ated exciting new possibilities to capitalize on the strengths of
EEG to improve our understanding of brain behavior. From a
clinical perspective, furthering the science of brain behavior
supporting motor recovery has the potential to improve rehabil-
itation outcomes by facilitating the development of sensitive
measures to predict and monitor recovery trajectories, iden-
tification of the salient neural substrates underlying specific
functional impairments, and selection of interventions on the
basis of individual characteristics of abnormal brain behavior
associated with neurologic disorders such as stroke.
ACKNOWLEDGMENTS
We thank Drs Scott Makeig and Makoto Miyakoshi for
consultation and assistance with aspects of data analysis. We
also thank Sue Peters and Nick Snow for providing images for
inclusion in this work.


C 2015 Neurology Section, APTA 49

Copyright © 2015 Neurology Section, APTA. Unauthorized reproduction of this article is prohibited.
Borich et al
REFERENCES
1. Berger H. Uber das Elektroenkephalogramm des Menschen. Arch Psychi-
atr Nervenkr 1929;87:527-570.
2. Patterson MM, Thompson RF. Bioelectric Recording Techniques. New
York, NY: Academic Press; 1973.
3. Nunez PL. Electric Fields of the Brain: The Neurophysics of EEG. New
York, Oxford: Oxford University Press; 2006.
4. Peterson NN, Schroeder CE, Arezzo JC. Neural generators of early cor-
tical somatosensory evoked potentials in the awake monkey. Electroen-
cephalogr Clin Neurophysiol. 1995;96(3):248-260.
5. TallonBaudry C, Bertrand O, Delpuech C, Pernier J. Oscillatory gamma-
band (30-70 Hz) activity induced by a visual search task in humans. J.
Neurosci. 1997;17(2):722-734.
6. Cohen MX, Elger CE, Ranganath C. Reward expectation mod-
ulates feedback-related negativity and EEG spectra. Neuroimage.
2007;35(2):968-978.
7. Praamstra P, Boutsen L, Humphreys GW. Frontoparietal control of
spatial attention and motor intention in human EEG. J Neurophysiol.
2005;94(1):764-774.
8. Litt B, Echauz J. Prediction of epileptic seizures. Lancet Neurol.
2002;1(1):22-30.
9. Spencer KM, Nestor PG, Niznikiewicz MA, Salisbury DF, Shenton ME,
McCarley RW. Abnormal neural synchrony in schizophrenia. J Neurosci.
2003;23(19):7407-7411.
10. Ferrarelli F, Massimini M, Sarasso S, et al. Breakdown in cortical effective
connectivity during midazolam-induced loss of consciousness. Proc Natl
Acad Sci USA. 2010;107(6):2681-2686.
11. Riemann D, Spiegelhalder K, Feige B, et al. The hyperarousal model
of insomnia: a review of the concept and its evidence. Sleep Med Rev
2010;14(1):19-31.
12. Fernandez-Bouzas A, Harmony T, Bosch J, et al. Sources of abnormal
EEG activity in the presence of brain lesions. Clin Electroencephalogr.
1999;30(2):46-52.
13. Cruse D, Chennu S, Chatelle C, et al. Bedside detection of awareness in
the vegetative state: a cohort study. Lancet. 2011;378(9809):2088-2094.
14. Cuspineda E, Machado C, Aubert E, Galan L, Llopis F, Avila Y. Predicting
outcome in acute stroke: a comparison between QEEG and the Canadian
Neurological Scale. Clin Electroencephalogr. 2003;34(1):1-4.
15. Blackwood DH, Muir WJ. Cognitive brain potentials and their application.
Br J Psychiatry Suppl. 1990(9):96-101.
16. Sur S, Sinha VK. Event-related potential: an overview. Ind Psychiatry J.
2009;18(1):70-73.
17. Schiff ND, Nauvel T, Victor JD. Large-scale brain dynamics in disorders
of consciousness. Curr Opin Neurobiol. 2014;25:7-14.
18. Knyazev GG. EEG delta oscillations as a correlate of basic homeostatic
and motivational processes. Neurosci Biobehav Rev. 2012;36(1):677-695.
19. Woertz M, Pfurtscheller G, Klimesch W. Alpha power dependent light
stimulation: dynamics of event-related (de)synchronization in human elec-
troencephalogram. Brain Res Cogn Brain Res. 2004;20(2):256-260.
20. Steriade M. Cellular Substrates of Brain Rhythms. Philadelphia, PA:
Lippincott Williams & Wilkins; 2005.
21. Bruns A, Eckhorn R. Task-related coupling from high- to low-frequency
signals among visual cortical areas in human subdural recordings. Int J
Psychophysiol. 2004;51(2):97-116.
22. Devrim M, Demiralp T, Ademoglu A, Kurt A. A model for P300 genera-
tion based on responses to near-threshold visual stimuli. Brain Res Cogn
Brain Res 1999;8(1):37-43.
23. Schurmann M, Basar-Eroglu C, Kolev V, Basar E. Delta responses and
cognitive processing: single-trial evaluations of human visual P300. Int J
Psychophysiol. 2001;39(2-3):229-239.
24. Roehm D, Schlesewsky M, Bornkessel I, Frisch S, Haider H. Fractionating
language comprehension via frequency characteristics of the human EEG.
Neuroreport. 2004;15(3):409-412.
25. Kahana MJ, Seelig D, Madsen JR. Theta returns. Curr Opin Neurobiol.
2001;11(6):739-744.
26. Fell J, Klaver P, Elfadil H, Schaller C, Elger CE, Fernandez G. Rhinal-
hippocampal theta coherence during declarative memory formation: in-
teraction with gamma synchronization? Eur J Neurosci. 2003;17(5):1082-
1088.
27. Klimesch W, Doppelmayr M, Stadler W, Pollhuber D, Sauseng P, Rohm
D. Episodic retrieval is reflected by a process specific increase in human
electroencephalographic theta activity. Neurosci Lett. 2001;302(1):49-52.
50
Copyright © 2015 Neurology Section, APTA. Unauthorized reproduction of this article is prohibited.
JNPT r Volume 39, January 2015
28. Klimesch W, Doppelmayr M, Yonelinas A, et al. Theta synchronization
during episodic retrieval: neural correlates of conscious awareness. Brain
Res Cogn Brain Res. 2001;12(1):33-38.
29. Lopes da Silva FH, Vos JE, Mooibroek J, Van Rotterdam A. Relative
contributions of intracortical and thalamo-cortical processes in the gener-
ation of alpha rhythms, revealed by partial coherence analysis. Electroen-
cephalogr Clin Neurophysiol. 1980;50(5-6):449-456.
30. Klimesch W. EEG alpha and theta oscillations reflect cognitive and
memory performance: a review and analysis. Brain Res Brain Res Rev.
1999;29(2-3):169-195.
31. Klimesch W, Sauseng P, Hanslmayr S. EEG alpha oscillations: the
inhibition-timing hypothesis. Brain Res Rev. 2007;53(1):63-88.
32. Salenius S, Hari R. Synchronous cortical oscillatory activity during motor
action. Curr Opin Neurobiol. 2003;13(6):678-684.
33. Neuper C, Pfurtscheller G. Event-related dynamics of cortical rhythms:
frequency-specific features and functional correlates. Int J Psychophysiol.
2001;43(1):41-58.
34. Bekisz M, Wrobel A. Attention-dependent coupling between beta activi-
ties recorded in the cat’s thalamic and cortical representations of the central
visual field. Eur J Neurosci. 2003;17(2):421-426.
35. Kahana MJ. The cognitive correlates of human brain oscillations. J Neu-
rosci. 2006;26(6):1669-1672.
36. Sauseng P, Klimesch W. What does phase information of oscillatory
brain activity tell us about cognitive processes? Neurosci Biobehav Rev.
2008;32(5):1001-1013.
37. Palva JM, Palva S, Kaila K. Phase synchrony among neuronal oscillations
in the human cortex. J Neurosci Methods. 2005;25(15):3962-3972.
38. Schack B, Vath N, Petsche H, Geissler HG, Moller E. Phase-coupling of
theta-gamma EEG rhythms during short-term memory processing. Int J
Psychophysiol. 2002;44(2):143-163.
39. Schack B, Weiss S. Quantification of phase synchronization phenom-
ena and their importance for verbal memory processes. Biol Cybern.
2005;92(4):275-287.
40. Sayers BM, Beagley HA, Henshall WR. The mechanism of auditory
evoked EEG responses. Nature. 1974;247(5441):481-483.
41. Başar E. Brain Function and Oscillations. New York, Berlin: Springer;
1998.
42. Luck SJ. An Introduction to the Event-Related Potential Technique. Cam-
bridge, MA: MIT Press; 2005.
43. Siebner HR, Bergmann TO, Bestmann S, et al. Consensus paper:
combining transcranial stimulation with neuroimaging. Brain Stimul.
2009;2(2):58-80.
44. Dale AM, Halgren E. Spatiotemporal mapping of brain activity by
integration of multiple imaging modalities. Curr Opin Neurobiol.
2001;11(2):202-208.
45. Delorme A, Makeig S. EEGLAB: an open source toolbox for analysis of
single-trial EEG dynamics including independent component analysis. J
Neurosci Methods. 2004;134(1):9-21.
46. Pascualmarqui RD, Michel CM, Lehmann D. Low-resolution electromag-
netic tomography—a new method for localizing electrical activity in the
brain. Int J Psychophysiol. 1994;18(1):49-65.
47. Michel CM, Murray MM, Lantz G, Gonzalez S, Spinelli L, de Peralta RG.
EEG source imaging. Clin Neurophysiol. 2004;115(10):2195-2222.
48. Taub E, Crago J, Burgio L, Groomes T, Cook EI, DeLuca S. An oper-
ant approach to rehabilitation medicine: overcoming learned nonuse by
shaping. J Exp Anal Behav. 1994;61:281-293.
49. Faught E. Current role of electroencephalography in cerebral ischemia.
Stroke. 1993;24(4):609-613.
50. Feys H, Van Hees J, Bruyninckx F, Mercelis R, De Weerdt W. Value of
somatosensory and motor evoked potentials in predicting arm recovery
after a stroke. J Neurol Neurosurg Psychiatry. 2000;68(3):323-331.
51. Gott PS, Karnaze DS, Fisher M. Assessment of median nerve somatosen-
sory evoked potentials in cerebral ischemia. Stroke. 1990;21(8):1167-
1171.
52. Zeman BD, Yiannikas C. Functional prognosis in stroke: use of
somatosensory evoked potentials. J Neurol Neurosurg psychiatry.
1989;52(2):242-247.
53. Macdonell RA, Donnan GA, Bladin PF. A comparison of somatosensory
evoked and motor evoked potentials in stroke. Ann Neurol. 1989;25(1):
68-73.
54. Giaquinto S, Cobianchi A, Macera F, Nolfe G. EEG recordings in the
course of recovery from stroke. Stroke. 1994;25(11):2204-2209.

C 2015 Neurology Section, APTA
JNPT r Volume 39, January 2015
55. Stojanovic B, Djurasic L. Predictive importance of index of asym-
metry in recovery following stroke. Acta Chir Iugosl. 2013;60(1):
101-104.
56. Cuspineda E, Machado C, Galan L, et al. QEEG prognostic value in acute
stroke. Clin EEG Neurosci. 2007;38(3):155-160.
57. Sheorajpanday RV, Nagels G, Weeren AJ, van Putten MJ, De Deyn PP.
Quantitative EEG in ischemic stroke: correlation with functional status
after 6 months. Clin Neurophysiol. 2011;122(5):874-883.
58. Platz T, Kim IH, Pintschovius H, et al. Multimodal EEG analysis in man
suggests impairment-specific changes in movement-related electric brain
activity after stroke. Brain. 2000;123(pt 12):2475-2490.
59. de Vico Fallani F, Astolfi L, Cincotti F, et al. Evaluation of the brain
network organization from EEG signals: a preliminary evidence in stroke
patient. Anat Rec. 2009;292(12):2023-2031.
60. Wu W, Sun J, Jin Z, et al. Impaired neuronal synchrony after focal ischemic
stroke in elderly patients. Clin Neurophysiol. 2011;122(1):21-26.
61. Dean PJ, Seiss E, Sterr A. Motor planning in chronic upper-limb
hemiparesis: evidence from movement-related potentials. PLoS One.
2012;7(10):e44558.
62. Birbaumer N, Cohen LG. Brain-computer interfaces: communication
and restoration of movement in paralysis. J Physiol. 2007;579(pt 3):
621-636.
63. Birbaumer N, Murguialday AR, Cohen L. Brain-computer interface in
paralysis. Curr Opin Neurol. 2008;21(6):634-638.
64. Hinterberger T, Widman G, Lal TN, et al. Voluntary brain regulation
and communication with electrocorticogram signals. Epilepsy Behav
2008;13(2):300-306.
65. Ramos-Murguialday A, Broetz D, Rea M, et al. Brain-machine inter-
face in chronic stroke rehabilitation: a controlled study. Ann Neurol.
2013;74(1):100-108.
66. Yeom H, Chang YH. Autogenic EMG-controlled functional electri-
cal stimulation for ankle dorsiflexion control. J Neurosci Methods.
2010;193(1):118-125.
67. Rohrbaugh JW, Syndulko K, Lindsley DB. Brain wave components of the
contingent negative variation in humans. Science 1976;191(4231):1055-
1057.
68. Walter WG, Cooper R, Aldridge VJ, McCallum WC, Winter AL. Contin-
gent negative variation: an electric sign of sensorimotor association and
expectancy in the human brain. Nature 1964;203:380-384.
69. Geocadin RG, Ghodadra R, Kimura T, et al. A novel quantitative
EEG injury measure of global cerebral ischemia. Clin Neurophysiol.
2000;111(10):1779-1787.
70. Finnigan SP, Rose SE, Walsh M, et al. Correlation of quantitative EEG in
acute ischemic stroke with 30-day NIHSS score: comparison with diffu-
sion and perfusion MRI. Stroke. 2004;35(4):899-903.
71. Finnigan S, van Putten MJ. EEG in ischaemic stroke: quantitative EEG
can uniquely inform (sub-) acute prognoses and clinical management. Clin
Neurophysiol. 2013;124(1):10-19.
72. Schleiger E, Sheikh N, Rowland T, Wong A, Read S, Finnigan S.
Frontal EEG delta/alpha ratio and screening for post-stroke cognitive
deficits: the power of four electrodes. Int J Psychophysiol. 2014;94(1):
19-24.

C 2015 Neurology Section, APTA
Copyright © 2015 Neurology Section, APTA. Unauthorized reproduction of this article is prohibited.
Applications of Electroencephalography to Characterize Brain Activity
73. Gerloff C, Bushara K, Sailer A, et al. Multimodal imaging of brain reorga-
nization in motor areas of the contralesional hemisphere of well recovered
patients after capsular stroke. Brain. 2006;129(pt 3):791-808.
74. Vuckovic A. Hybrid brain-computer interface and functional electrical
stimulation for sensorimotor training in participants with tetraplegia: A
proof-of-concept study. J Neuro Phys Ther, 2015;39:3-14.
75. Takahashi M, Takeda K, Otaka Y, et al. Event related desynchronization-
modulated functional electrical stimulation system for stroke rehabilita-
tion: a feasibility study. J Neuroeng Rehabil. 2012;9:56.
76. Day BL, Dick JPR, Marsden CD, et al. Interaction between electrical and
magnetic stimulation of the human brain. J Physiol 1987;384:74P.
77. Thickbroom GW, Byrnes ML, Archer SA, Mastaglia FL. Motor outcome
after subcortical stroke: MEPs correlate with hand strength but not dex-
terity. Clin Neurophysiol. 2002;113(12):2025-2029.
78. Liepert J, Storch P, Fritsch A, Weiller C. Motor cortex disinhibition in
acute stroke. Clin Neurophysiol. 2000;111:671-676.
79. Liepert J, Hamzei F, Weiller C. Motor cortex disinhibition of the unaf-
fected hemisphere after acute stroke. Muscle Nerve. 2000;23:1761-1763.
80. Butefisch CM, Netz J, Wessling M, Seitz RJ, Homberg V. Remote changes
in cortical excitability after stroke. Brain 2003;126(pt 2):470-481.
81. Murase N, Duque J, Mazzocchio R, Cohen LG. Influence of interhemi-
spheric interactions on motor function in chronic stroke Ann Neurol.
2004;55:400-409.
82. Ward NS, Cohen LG. Mechanisms underlying recovery of motor function
after stroke. Arch Neurol. 2004;61(12):1844-1848.
83. Lioumis P, Kicic D, Savolainen P, Mäkelä JP, Kähkönen S. Reproducibil-
ity of TMS-evoked EEG responses. Hum Brain Mapp. 2009;30(4):1387-
1396.
84. Komssi S, Aronen HJ, Huttunen J, et al. Ipsi- and contralateral
EEG reactions to transcranial magnetic stimulation. Clin Neurophysiol.
2002;113(2):175-184.
85. Ferrarelli F, Massimini M, Peterson MJ, et al. Reduced evoked gamma
oscillations in the frontal cortex in schizophrenia patients: a TMS/EEG
study. Am J Psychiatry. 2008;165(8):996-1005.
86. Stinear CM, Barber PA, Smale PR, Coxon JP, Fleming MK, Byblow WD.
Functional potential in chronic stroke patients depends on corticospinal
tract integrity. Brain. 2007;130(pt 1):170-180.
87. Ilmoniemi RJ, Virtanen J, Ruohonen J, et al. Neuronal responses to mag-
netic stimulation reveal cortical reactivity and connectivity. Neuroreport.
1997;8(16):3537-3540.
88. Farzan F, Barr MS, Hoppenbrouwers SS, et al. The EEG correlates of the
TMS-induced EMG silent period in humans. Neuroimage. 2013;83:120-
134.
89. Hoppenbrouwers SS, Farzan F, Barr MS, et al. Personality goes a
long a way: an interhemispheric connectivity study. Front Psychiatry.
2010;1:140.
90. Leamy DJ, Kocijan J, Domijan K, et al. An exploration of EEG fea-
tures during recovery following stroke—implications for BCI-mediated
neurorehabilitation therapy. J Neuroeng Rehabil. 2014;11(1):9.
91. Machado S, Araujo F, Paes F, et al. EEG-based brain-computer interfaces:
an overview of basic concepts and clinical applications in neurorehabili-
tation. Rev Neurosci. 2010;21(6):451-468.
51