Neurocase (2006) 12, 322–331

Copyright © Taylor & Francis Group, LLC

ISSN: 1355-4795 print / 1465-3656 online
DOI: 10.1080/13554790601126054

Functional Imaging Before and After Constraint-Induced

NNCS

Language Therapy for Aphasia Using Magnetoencephalography

JOSHUA I. BREIER1, LYNN M. MAHER2, BARBRA NOVAK3 and ANDREW C. PAPANICOLAOU1

Brain Plasticity in Aphasia Therapy Using MEG

1
Division of Clinical Neurosciences in the Department of Neurosurgery, University of Texas – Houston Health Science Center, Houston,
Texas, USA
2
Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, Texas, USA
3
Rice University, Department of Linguistics, Houston, Texas, USA

Five patients with chronic aphasia underwent functional imaging using magnetoencephalography (MEG) before and after constraint-
induced language therapy (CILT). Patients who responded well to CILT exhibited a greater degree of late MEG activation in posterior
language areas of the left hemisphere and homotopic areas of the right hemisphere prior to therapy than those who did not respond well.
Response to CILT, however, was positively correlated with the degree of pre-therapy MEG activity within posterior areas of the right
hemisphere only on an individual basis.

Chronic communicative impairment, or aphasia, may occur
in 20% or more of patients after stroke (e.g., Kertesz, 1984;
Pedersen et al., 1995). Knowledge of the brain mechanisms
that contribute to recovery of language in aphasic patients has
the potential for providing a basis for the design and evalua-
tion of rehabilitation strategies. In this regard, the recent
emergence of non-invasive functional imaging methods pro-
vides the opportunity to index the physiological conse-
quences of plastic changes in the brain in response to
therapeutic intervention, and to correlate these with changes
in behavioral deficit. In the current study we present data
regarding the changes in language-specific brain activity in
5 patients with chronic aphasia who underwent magnetoen-
cephalographic (MEG) mapping of language cortex both
prior and subsequent to the administration of constraint-
induced language therapy (CILT). CILT is an intervention for
aphasia based on constraint principles of forced use, massed
practice, and shaping of behavior (Taub, 2004). Applied to
aphasia, these same principles have been shown to have a
positive effect on recovery and use of verbal output in
patients with chronic aphasia (Maher et al., in press; Meinzer,
et al., 2005; Pulvermuller et al., 2001).
Received 19 May 2006; accepted 16 Novemeber 2006.
This work was supported by NIH/NINDS Grant #P51-NS046588
to A.C. Papanicolaou and the Vivian L. Smith Center for Neurolog-
ic Research. The authors wish to thank Stephanie Schmadeke for
her assistance with this project, and our volunteers with aphasia for
the invaluable contribution of their time and effort.
Address correspondence to Joshua I. Breier, PhD, Department of
Neurosurgery, Division of Clinical Neurosciences, University of
Texas – Houston Health Science Center, 1333 Moursund Street,
Suite H114, Houston, Texas 77030, USA. E-mail: Joshua.i.breier
@uth.tmc.edu
Functional imaging studies indicate relative increases in
electrophysiological (Papanicolaou et al., 1987; Papanico-
laou, et al., 1988), metabolic (Heiss et al., 1999; Karbe et al.,
1998) and hemodynamic response in the right hemisphere of
post-left hemisphere stroke patients with aphasia during per-
formance of linguistic tasks. Recent studies, however, sug-
gest that increases in activity within the right hemisphere in
aphasic patients, at least during some tasks, may be related to
transcallosal disinhibition rather than direct support of lan-
guage function (e.g., Fernandez et al., 2004; Naeser et al.,
2004; Xu et al., 2004). The role of the right hemisphere in
language recovery may become significant only when lan-
guage areas in the left hemisphere are destroyed, and reacti-
vation of pre-morbid language areas or areas surrounding
pre-morbid language areas that are able to support language
function in the left hemisphere may result in the best recov-
ery (Breier et al., 2004; Heiss et al., 1999; Perani et al.,
2003).
While the number of functional imaging studies document-
ing changes in brain activation following therapy for aphasia is
limited, most suggest some degree of increase in activation
within the right hemisphere in response to therapy. Musso
et al. (1999) found a correlation between improvement in com-
prehension and increased blood flow in right superior temporal
gyrus following therapy in four patients with chronic aphasia.
Peck et al. (2004) found evidence for normalization of the tim-
ing of hemodynamic response in the right hemisphere homo-
logue of Broca’s area in 2 of 3 aphasic patients after treatment
that resulted in increased speed of word-finding. Crosson et al.
(2005) found evidence for a role for the dominant basal ganglia
in reorganization of language function to the right hemisphere.
In contrast to these studies suggesting right hemisphere partici-
pation in recovery of function, Meizner et al. (2004), using
MEG, found evidence for increased connectivity in areas
Brain Plasticity in Aphasia Therapy Using MEG 323
surrounding the lesion within the dominant hemisphere and Table 1. Demographic Variables
improvement in language function after therapy.
Months
In the current study we use MEG methods to index the rel-
Patient Post
ative engagement of cortical areas that may potentially serve Number Age Education Gender Stroke L PTA R PTA
as a substrate for language recovery. This methodology was
developed and validated in a programmatic series of experi- P1 53 1 year M 70 25 20
ments in neurologically intact controls and patients with of college
chronic seizure disorder that demonstrated that: (1) the task P2 58 5 years M 48 38 23
employed (identifying which words in a list were previously of college
presented in either auditory or visual modalities) can activate P3 77 2 years F 27 26 28
of college
language-specific cortex; (2) this language-specific activation
P4 66 High School M 68 36 43
is reflected in the late components (after the resolution of the Diploma
N1m) of the event-related fields (ERFs) to the words, P5 56 High School M 21 28 21
whether target or foil; (3) the mathematical model for esti- Diploma
mating the sources of those components (i.e. identifying the 1 year
P6 58 F 47 33 25
activated brain areas) is sufficiently valid; and (4) the dura- of college
tion of late activation (or number of thresholded sources) thus
L=Left ear, R=R ear, PTA=pure tone average.
identified is a valid index of the relative degree of engagement
of a particular brain area (Breier et al., 1999; Breier, et al.,
2000; Breier et al., 2001; Papanicolaou et al., 1999a. 1999b; Participants were recruited through professional referrals
Simos et al., 1999; Simos et al., 2001; Zouridakis, et al., 1998). and study brochures at the University of Texas Health Sci-
Previous research by our group using similar MEG method- ence Center (UTHSC) and the Michael E. DeBakey VA
ology in patients with chronic aphasia suggests that language Medical Center (MEDVAMC), Houston, TX. The study was
function is related to the degree of activation of pre-morbid approved and monitored by the respective Institutional
language and peri-lesional areas capable of supporting lan- Review Boards and the MEDVA research subcommittee. All
guage function in the left hemisphere (Breier et al., 2004). participants provided informed consent prior to participation.
Based on our previous results, as well as those of other All participants presented with a persistent moderate to
researchers, we hypothesized that improvement in language severe aphasia as indicated by the Western Aphasia Battery
function after CILT would be associated with an increase in (Kertesz, 1982) exhibiting deficits in expressive and recep-
late (after the resolution of the N1m) MEG activation, as well tive language. In addition, all presented with significant word
as the normalization of the temporal parameters of this activ- retrieval deficits as indicated by the Boston Naming Test
ity, in or around putative pre-morbid language areas in the left (Kaplan, et al., 2000) and varying degrees of apraxia of
hemisphere. While we expected there might be an increase in speech as measured by the Apraxia Battery for Adults-2,
activation in homotopic areas of the right hemisphere we did (DaBul, 2000) (see Table 2 for pre-and post-treatment speech
not expect this change to be related to functional status. and language characteristics).

Methods
Participants: Participants were 6 premorbidly right-handed
individuals ranging in age from 53 to 77 years (M=62.0,
SD=9.7). While all 6 subjects received MEG and underwent
CILT, the MEG data from 1 participant, P6, exhibited signifi-
cant noise contamination which appeared to stem from exten-
sive dental work and precluded MEG analysis. All
participants had a history of first-ever ischemic stroke in the
territory of the left middle cerebral artery, were at least 1 year
post-stroke, and were right-handed pre-morbidly as assessed
with the Edinbugh Handedness Inventory (Oldfield, 1971).
All patients were given standard audiometric screening at 500,
1000, 2000 Hz (ANSI, 2004). As expected, hearing loss
ranged from mild to the low end of the moderate range. Corre-
lations between pure tone averages and peak of late MEG acti-
vation in either hemisphere were not significant. Demographic
and hearing data for each patient are presented in Table 1.
CILT Methods
CILT Intervention
CILT was administered following the procedures described
by Pulvermüller et al. (2001) as adapted more recently by
Maher et al. (in press). Therapy was conducted in dyads of
participants, and consisted of 3-hour sessions, 4 days a week,
for 3 weeks for a total of 36 hours of treatment. Constraint
was operationally defined as limiting the response to spoken
verbal production only. All other modes of communication
were restrained, even as related to self-cuing. The forced use
of spoken communication was accomplished by placing
a visual barrier on the table between the participants so they
could not see each other except for eye contact. This barrier
forced the participants to use the spoken modality to accom-
plish the interaction, similar to when talking on a telephone.
As in the Maher et al. (in press) study, the primary treat-
ment task was a dual card task. Each participant took turns
either requesting a matching card to one in their hand from
324 J.I. Breier et al.
Table 2. Speech and Language Characteristics Pre- and Post-therapy

Auditory
Repetition Comprehension % Accuracy on TX % CIUs on TX
(WAB) (WAB) WAB AQ BNT response probe response probe
Patient
Number pre post pre post pre post pre post pre post pre post Aphasia DX
P1 4.5 5.6 8.5 8.4 65.0 72.4 33 42 3 90 56 98 Broca’s
P2 7.4 8 9.25 9.05 74.7 76.3 50 48 11 63 72 91 Broca’s
P3 5.8 7.1 8.5 9.4 72.8 80.6 53 46 5 61 61 91 Conduction
P4 5.7 2.6 7 7 46.8 39.6 7 1 0 0 3 3 Broca’s
P5 0.8 0.8 6.1 6.1 23.6 25.2 0 1 0 0 6 13 Broca’s
P6 2.2 2.3 6.7 6.4 30.4 32.6 1 0 0 0 23 59 Broca’s
WAB=Western Aphasia Battery; Repetition and Auditory Comprehension scores are out of a possible score of 10; AQ=Aphasia Quotient, # correct out of
100; BNT=Boston Naming Test, # correct out of 60; CIUs=Correct Information Units; TX=treatment; DX=diagnosis.

a semantic category from the other participant, or responding
to their partner’s request. There were 4 sets of cards of differ-
ent semantic categories used in therapy, and a fifth category
reserved to assess generalization. Each semantic category had
two levels of difficulty; high frequency words and low fre-
quency words.
An additional component of the CILT intervention mod-
eled after CIMT included a strategy called shaping (Taub,
2004). This concept is grounded in operant training principles
and refers to the gradual, successive approximation of behav-
ior in small steps toward the desired goal. In this study, shap-
ing entailed increasing the communicative demands of the
required request/response from single words to lengthy sen-
tences. Each set of cards contained pictures with increasing
amounts of detail. As the participants improved in their abil-
ity to request and respond using the simple cards (e.g., “Bill,
do you have a book?”) the more detailed cards were used,
which I turn required more lengthy, detailed output (e.g.,
“Bill, do you have a red book?” and “Bill, do you have three
red books?”). Once the participants were successful with the
most detailed, high-frequency cards, these stages were
repeated using the low-frequency cards.
The therapist provided as much cuing as necessary (indi-
vidualized for each participant) for a successful response. In
all cases, the participants ended each trial with a successful
response, using whatever means necessary (e.g., phonemic or
semantic cuing, repetition, etc.). The amount of support pro-
vided was gradually reduced based on the participants’ needs.
At all times participants were constrained to using only spo-
ken communication in therapy. They were encouraged to
continue with using only spoken communication as much as
possible outside of the therapy session.
TX Response measure
Performance on the dual card task was used as the TX
response measure. Baseline performance on this task was
obtained for each participant on three consecutive days to
establish a reliable baseline performance prior to the initia-
tion of treatment. Each response was coded for the number of
bits of information correctly conveyed, in a modification of
Nicholas and Brookshire’s (1993) Correct Information Units
(CIUs). In this modification, the question phrase (e.g., “Do
you have” or “Can you give me” was collectively scored as 1
CIU, rather than counting each word in the phrase as an infor-
mation unit. Each baseline consisted of twenty card requests
and the % CIUs for each baseline was calculated. Three con-
secutive baselines were obtained at the conclusion of therapy
and the pre-to-post TX baselines were compared for change
in % CIUs.
Reliability
All testing and 20% of the treatment sessions were video-
taped for reliability purposes. All standard aphasia tests were
scored by at least two investigators for accuracy. A separate
therapist who was not involved in the treatment viewed the
taped sessions to ensure treatment fidelity.
CILT Results
All 6 subjects demonstrated progress, as indicated by their
ability to increase from 2 CIU-utterances to 5-CIU utterances
during therapy. However, substantial change of 25% or more
from pre-TX to post-TX on the treatment response measure
indicating a good treatment response was observed in only
3 of the 6 participants (P1, P3, and P6). A fourth participant,
P2, increased performance 19% on the CIU measure, sug-
gesting a moderate treatment response. These results are
presented in Table 2.
MEG Methods
Stimuli and tasks
Five of the 6 particpants were able to particpate in the MEG
imaging protocol. Participants were given a recognition
memory task for spoken words and event-related fields
(ERFs) were recorded to each word stimulus. The word list
consisted of 165 English words, including nouns, adjectives,
and verbs, generally one or two syllables in length. A native
Brain Plasticity in Aphasia Therapy Using MEG
speaker of English with a flat intonation produced the audi-
tory stimuli. Stimuli were digitized with a sampling rate of
22,000 Hz and 16-bit resolution and delivered binaurally via
two 5 m-long plastic tubes terminating in ear inserts. Five
words were used as targets and the remaining 160 as distrac-
tors in each list. Four blocks of 45 trials each were created
with the 5 targets presented in random order in each among
40 new distractors in each block for a total of 180 trials. Two
separate blocks of trials were obtained at different time points
and spatiotemporal parameters of MEG activation were aver-
aged across the 2 sessions.
The target stimuli were presented for study immediately
prior to the MEG scan and participants entered into the scan-
ning phase after being able to raise their left index finger after
the presentation of each of the 5 targets. During this initial
training period an attempt was made to match stimulus inten-
sity bilaterally by delivering the signal at 80 dB to both outer
ears and having the examiner increase the signal in the ear
with the greatest degree of hearing loss until the patient indi-
cated that the words were perceived as coming from the
middle of the head.
Stimulus presentation parameters were identical during the
actual recording and training sessions. Stimuli were pre-
sented with a variable interstimulus interval (2.5–3.5 sec).
Patients were asked to lift their left index finger whenever
they detected a target word as during the training session.
During the entire testing session the patient was asked to
keep his/her eyes open, fixating on a dark dot placed on the
ceiling at eye level, in order to reduce eye movements or
blinks and prevent ERF contamination by rhythmic activity
(typically in the alpha band) which can seriously interfere
with the accurate detection of task-related brain activity.
Correct response rate was low (13%), while false positive
rate was relatively high (10 %). This was not totally unex-
pected as patients had a range of language difficulties. There
were no significant correlations between rate of correct or
false positive responses during MEG scanning or hearing
screening and MEG variables reported on below.
MEG data acquisition and analysis
ERFs time-locked to the words were recorded in a magneti-
cally shielded room using a whole-head neuromagnetometer
(4D 3600, 4D NeuroImaging, San Diego) equipped with an
array of 248 gradiometer sensors and housed in a magneti-
cally shielded room designed to reduce environmental mag-
netic noise that might interfere with biological signals. The
typical recording session required the patient to lie motion-
less on a bed with his or her head inside the helmet-like
device for approximately 15 minutes. The signal was
recorded with a band pass filter set at 0.1 and 50 Hz, and dig-
itized for 1000 ms (254 Hz sampling rate) including a 150 ms
pre-stimulus period.
All of the post-collection analysis of the MEG recordings
was performed by an automated program. Single-trial
ERF segments identified as contaminated by eye- or head-
325
movement related magnetic artifacts (defined as magnetic
flux deflections in excess of 3 picoTesla (pT) peak-to-peak in
the recordings from magnetometer sensors placed just above
the eyes) were removed and the recordings were filtered with
a band pass between 0.1 and 20 Hz, and subjected to an adap-
tive filtering procedure that is part of the 4-D Neuroimaging
signal analysis package. Artifact-free epochs in each channel
were subsequently averaged.
The intracranial generators, or activity sources, of the aver-
aged waveforms were modeled as single equivalent current
dipoles (ECD) and fitted at successive 4 ms intervals (Sarvas,
1987). Channel-groups were chosen for gradients calculated
at successive 4 ms intervals between 40 ms and 1000 ms
post-stimulus onset. In general, sources are located below the
maxima of the planar gradients of the field. Center channels
of the channel groups were selected based on the local max-
ima of the calculated gradient pattern. Up to 5 could be
selected at each time point. Any maxima that were less that
10% of the strongest maxima were rejected. For each candi-
date maximum its width was estimated using a 2-D Gaussian
function and that width was compared to the widths of max-
ima from theoretical dipole sources that had been generated
from a simple spherical model. This adjustment was limited
such that the radius of the resulting channel-group was
always greater than 7 cm and less than 9.5 cm. From this
comparison the extent of the channel-group was determined.
Finally, to help reject maxima that would often occur near the
edge of the array due to edge effects the resulting channel
group was inspected to make sure it extended across a zero
line in the filed data. If either the number channels having
positive, or negative field values was less than 10% of the
total number of channels the group was rejected. Source solu-
tions were considered satisfactory if they were associated
with a correlation coefficient of at least 0.9 between the
observed and the “best” predicted magnetic field distribution
with a confidence interval of 20 mm or less.
Source locations, which were initially computed in refer-
ence to the MEG Cartesian coordinate system mentioned
above, were co-registered on the T1-weighted, magnetic res-
onance image (MRI) (TR 13.6 ms; TE 4.8 ms; recording
matrix 256 × 256 pixels, 1 excitation, 240 mm field of view,
and 1.4 mm slice thickness) obtained from the participant.
Transformation of the MEG coordinate system into MRI-
defined space was achieved with the aid of 3 lipid capsules
inserted into the ear canals and attached to the nasion which
were easily visualized on the MRIs, using the MRI Overlay
tool which is part of the 4-D Neuroimaging software. Loca-
tion of individual dipoles was determined with the use of
a standard MRI atlas of the human brain (Damasio, 1995).
Results
Co-registered MEG – MRI scans for each participant both
before and after CILT are displayed in Figure 1. Mesial tem-
poral activation is not included. Consistent with our previous
326
Fig. 1. Co-registered MEG – MRI scans depicting cortical activation during the late epoch (after the resolution of the N1m) in the left
(yellow circles) and right (red circles) hemispheres both prior to (top scan) and after (bottom scan) CILT for 5 patients. Patients who
responded well to CILT were P1, P2, and P3. Patients who responded relatively less well were P4 and P5.
findings using similar methodology (Breier, et al. 2004), acti-
vation within the left hemisphere tends to be in expected lan-
guage areas (posterior superior and middle temporal gyri,
inferior parietal areas including angular and supramarginal
gyrus, and inferior frontal gyrus), or, when damage to these
areas is too severe, in tissue that is at the margin of the
ischemic lesion, but still near putative pre-morbid language
areas. Activation within the right hemisphere is generally
within areas homotopic to putative pre-morbid language
areas within the left hemisphere.
Relation between the effects of therapy and parameters of
MEG activation
Participants were divided into 2 groups, Responders (P1, P2,
P3) and Non-Responders (P4, P5), based on whether they
exhibited a significant response to therapy (see Table 2). Late
(after the resolution of the N1m) MEG activation in superior,
middle, and inferior temporal gyri, and supramarginal and
angular gyri was collapsed within hemisphere as Posterior
activation, while late activation within inferior frontal gyrus
and insula was collapsed as Anterior activation. Mean dura-
tion of late activation obtained during the pre-CILT scan
within Posterior and Anterior language areas within the left
hemisphere and homotopic areas within the right hemisphere
are presented for Responder and Non-Responder groups in
Figure 2. Responders exhibit greater activation than Non-
Responders within Posterior areas of both the left and right
hemispheres before the administration of CILT. Mean change
in duration of MEG activation within these areas after the
J.I. Breier et al.
administration of CILT is presented for each group in Figure 3.
Responders showed an increase in Anterior and decrease in
Posterior activation within the right hemisphere after CILT
compared to Non-Responders.
The relation between the degree of late MEG activation, as
measured by the total duration of this activity, and the response
to CILT as measured by change in accuracy and CIU (see
Table 2) was evaluated on an individual basis using Spearman
correlation coefficients. Significant correlations were found
between pre-CILT MEG activation in posterior areas of the
right hemisphere and change in accuracy (r=.87, p < .05),
change in CIUs (r=.90, p < .03) and change in WAB repetition
scores (r=1, p < .0001). Change in CIUs is plotted as a function
of the duration of late activity within posterior areas of the right
hemisphere that are homotopic to putative pre-morbid language
areas within the left hemisphere in Figure 4. The relationship
was similar for change in accuracy and repetition scores, indi-
cating that response to CILT increases with increasing pre-
therapy activation in these areas within the right hemisphere.
Data regarding the timing of the onset and peak latency, as
well as the peak, of the late MEG activity in both hemi-
spheres for Responder and Non-Responder groups are pre-
sented in Table 3. While all patients tended to experience an
increase in onset and peak latency within the left hemisphere
as compared to the right hemisphere after therapy, this trend
was exaggerated in the Non-Responders. Correlation analy-
ses similar to those performed above indicated a negative cor-
relation (r=−.71, p < .18) between the change in peak latency
in the left hemisphere and change in the WAB repetition
score after therapy. A similar relationship was found for
Brain Plasticity in Aphasia Therapy Using MEG 327
300

Mean Duration of Late Activity (ms)

250
Anterior
Posterior
200

150

100

50

0
Responders Non-Responders Responders Non-Responders

L Hemisphere R Hemisphere

Fig. 2. Degree (total duration in ms) of late activation prior to CILT in anterior (white bars) and posterior (gray bars) language areas within
the left hemisphere and homotopic areas within the right hemisphere for patients who responded well (Responders) and those that did not
respond as well (Non-Responders) to CILT.

250

200 Anterior
Posterior
150
Change in Activity Duration (ms)

100

50

-50

-100

-150

-200
Responders Non-Responders Responders Non-Responders

L Hemisphere R Hemisphere

Fig. 3. Change in degree (duration in ms) of late activation in anterior (white bars) and posterior (gray bars) language areas within the left
hemisphere and homotopic areas within the right hemisphere for patients who responded well (Responders) and those that did not respond
as well (Non-Responders) to CILT.

change in CIUs (r=−.7, p < .18) although significance was not ously shown to accurately lateralize and localize receptive
reached. Change in repetition score after therapy is plotted as language areas (Breier et al., 1999, 2001; Papanicolaou et al.,
a function of change in peak latency in the left hemisphere 2004; Simos et al., 1999a, 1999b, 2001) as well as parameters
Figure 5. These data indicate that response to CILT decreased of MEG activation shown to be sensitive to language func-
with an increase in peak latency within the left hemisphere. tion after stroke (Breier et al., 2004), we found that patients
who responded best to CILT exhibited greater activity in pos-
terior language areas within the left hemisphere and homo-
Discussion topic areas within the right hemisphere prior to therapy, and
that response to CILT was a function of the degree of pre-
Contrary to our hypotheses, CILT was not associated with therapy activation within the right, not the left, hemisphere.
normalization of activation within or near putative language Response to CILT was also associated with an increase, rather
areas within the left hemisphere. Using a paradigm previ- than a decrease, in latency of the peak of late activation within
328 J.I. Breier et al.

50

% Improvement in language (CIUs)

45

40

35

30

25

20

15

10

0
0 10 20 30 40 50 60 70 80
Mean number of late MEG dipoles

Fig. 4. Change in CIUs as a function of degree (duration in ms) of late activity of posterior areas within the right hemisphere prior to
therapy.

Table 3. Means and Standard Deviations for Temporal Parameters of Pre-CILT Late MEG Activity in Posterior Areas of the Left and Right
Hemispheres, and Change in These Parameters After CILT

Left Hemisphere Right Hemisphere

Responders Non-Responders Responders Non-Responders

Onset (ms post 267 159 162 195

stimulus onset)
SD 75 3 11 63
Peak latency (ms) 329 267 339 211
SD 87 104 62 79
Peak (fT) 72 99 65 71
SD 26 33 3 2
Onset change (ms) 74 234 23 −21
SD 91 115 47 151
Peak latency 199 556 −115 −14
change (ms)
SD 153 275 16 117
Peak change (fT) 51 −38 13 9
SD 30 37 14 12
ms=milliseconds; fT=femtotesla.

the left hemisphere after therapy, with reduced response to
CILT associated with greater increase in this latency.
A number of previous studies examining the effects of
therapy for chronic aphasia on brain activation suggest a pos-
sible role for the right hemisphere as a substrate for recovery
of language function (Crosson et al., 2005; Musso et al.,
1999; Peck et al., 2004). In many of the participants in these
studies change in behavioral measures correlated with
increased activation within the right hemisphere after ther-
apy. In contrast, in the current study we found that while
more severe aphasia was associated with reduced activation
bilaterally, change in performance after the administration of
CILT was positively correlated with the degree of activation
within the right hemisphere prior to therapy only. These find-
ings suggest that some degree of participation in language
function by the right hemisphere prior to therapy may facili-
tate the effects of CILT. Interestingly, the patient who
improved the least with CILT (P4, see Figure 1) exhibited the
Brain Plasticity in Aphasia Therapy Using MEG
3 with improved language performance. They interpreted
2 within areas that had been disconnected from functional
Change in WAB repetition score
1 incompatible with findings that implicate right hemisphere
0 wave activity that is generally confined to the dominant
0 100 200 300 400 500
-1
-2
-3
-4 Change in Peak Latency in LH
Fig. 5. Change in WAB repetition score as a function of change in
the peak latency of late activity of posterior areas within the left
hemisphere across therapy.
most significant increase in late activation of posterior areas
within the right hemisphere after CILT. One explanation for
these findings that is consistent with the overall results is that
a pre-morbid disposition to activation in right hemisphere is
necessary to support change in language function after
therapy, at least in the near term.
While the largest change overall across the CILT ses-
sions was in the anterior regions of the right hemisphere
of responders, much of this was due to a single subject,
P1, and the current study did not find a significant corre-
lation between changes in activation in the right hemi-
sphere and changes in language function after therapy.
There is a possibility, however, that a decrease in activity
may represent increased efficiency brought about by ther-
apy, and that the relation between activation and therapy
may not be linear, but rather change over time (e.g.,
Dobkin et al., 2004; Dong, et al., 2006.). Whether a
decrease in activity represents less participation or
increased efficiency might depend on the state of the sys-
tem at the start of therapy and the nature of change in the
neural substrates and therefore may differ from partici-
pant to participant. These issues cannot be fully addressed
in the current study, therefore blanket inferences regard-
ing the relative participation of either hemisphere in
recovery are not warranted. What is evident is a correla-
tion between pre-therapy activation in the right hemi-
sphere and response to therapy.
In contrast to findings suggesting a role for the right
hemisphere in recovery of function after therapy, Meinzer
et al. (2004) found evidence for changes in areas of the cor-
tex surrounding the lesion in affected hemisphere after ther-
apy. Meinzer et al. (2004) examined changes in the degree
of slow wave activity in the delta range in the affected
hemisphere and found that decreases in post-therapy delta
activity in areas near the margins of the lesion correlated
329
these data as indicating reconnection secondary to training
cortex by the stroke. These findings are not necessarily
involvement in recovery of function. By examining slow
600 700 800
hemisphere the Meinzer et al. (2004) study did not directly
address a potential role for the right hemisphere in response
to therapy. The contribution of the right hemisphere may be
in addition to that of the left hemisphere, or potentially in
response to activation within the left hemisphere. The func-
tional significance of neurophysiological changes in the
brain observed after language therapy remains a matter for
future research.
All patients experienced increased delay in the latency of
peak activation within posterior areas of the left hemisphere.
Correlation analyses analysis indicated that response to CILT
decreased with greater increase in this parameter. One expla-
nation for these findings may be a decrease in recruitment
within the left hemisphere with a potential corresponding
increase in recruitment in homotopic areas within the right
hemisphere in response to CILT. The evidence for the latter
possibility was not as salient as for the former, although 4 of
the 5 patients also exhibited a decrease in peak latency in
posterior areas of the right hemisphere concomitant with an
increase in peak latency within the left. This may potentially
represent disinhibition (Price and Crinion, 2005) and/or
functional change.
One of the goals of CILT is to increase the effectiveness
of spoken output. It is difficult, however, to image during
expressive language tasks using MEG because of muscle
artifact and the MEG task required no speech production.
Therefore, not all of the changes in activity relevant to
changes in patients’ expressive language due to therapy
may have been detected. In addition, many features of
brain activation associated with task performance in the
current study are likely missed by the single equivalent
dipole model that was used, which is applied to only that
fraction of the recorded activity that is suggestive of dipo-
lar sources. Other features in the data could possibly be
captured by alternative models such as multiple (e.g.,
Schwartz et al., 1999) and/or extended source models
(e.g., Liu et al., 1998, Moradi et al., 2003, Moran and
Tepley, 2000 and Mosher et al., 1999), some of which
have the desirable feature of taking into account the com-
plex geometry of the cortical surface (e.g., Moran and
Tepley, 2000; Mosher et al., 1999; Kober et al., 2003). Yet
none of these approaches have been subjected to external
validation of their accuracy in localizing intracranial activ-
ity sources as the single dipole model has (e.g., Papanico-
laou et al., 1999, Simos et al., 1999a, 1999b).
Given that the sample in the current study was small,
findings are preliminary in nature; however, they are con-
sistent with the possibility that, at least in some patients
with chronic aphasia, response to language therapy may
330
be related to the degree of activation of the right hemi-
sphere in response to linguistic stimulation prior to ther-
apy. Whether this represents functional participation or
the results of disinhibition is not clear, although the direc-
tion of the relationship with behavioral change across
therapy suggests the former. To address this issue, as well
as the stability and reliability of these findings, further
research with larger study samples as well as data from
consecutive post-therapy imaging and language testing
sessions is necessary.
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