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Published in final edited form as:
Brain Lang. 2010 April ; 113(1): 45–50. doi:10.1016/j.bandl.2010.01.001.

Stimulating Conversation: Enhancement of Elicited
Propositional Speech in a Patient with Chronic Nonfluent
Aphasia Following Transcranial Magnetic Stimulation
Roy H. Hamilton1,2, Linda Sanders2, Jennifer Benson2, Olufunsho Faseyitan2, Catherine
Norise3, Margaret Naeser4, Paula Martin4, and H. Branch Coslett1,2,5
1 Laboratory for Cognition and Neural Stimulation, Department of Neurology, University of
Pennsylvania
2 Center for Cognitive Neuroscience, University of Pennsylvania
3 Haverford College

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4 Harold Goodglass Boston University Aphasia Research Center, Department of Neurology,

Boston University School of Medicine and the Veterans Affairs Boston Healthcare System
5 Moss Rehabilitation Research Institute, Philadelphia

Abstract

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Although evidence suggests that patients with left hemisphere strokes and nonfluent aphasia who
receive 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the intact right inferior
frontal gyrus experience persistent benefits in naming, it remains unclear whether the effects of
rTMS in these patients generalize to other language abilities. We report a subject with chronic
nonfluent aphasia who showed stable deficits of elicited propositional speech over the course of
five years, and received 1200 pulses of 1 Hz rTMS daily for 10 days at a site identified as being
optimally responsive to rTMS in this patient. Consistent with prior studies there was improvement
in object naming, with a statistically significant improvement in action naming. Improvement was
also demonstrated in picture description at 2, 6, and 10 months after rTMS with respect to the
number of narrative words and nouns, sentence length, and use of closed class words. Compared
to his baseline performance, the patient showed significant improvement on the Western Aphasia
Battery subscale for spontaneous speech. These findings suggest that manipulation of the intact
contralesional cortex in patients with nonfluent aphasia may result in language benefits that
generalize beyond naming to include other aspects of language production.

Keywords
Interhemispheric interactions; language; TMS; inferior frontal gyrus; discourse; propositional
speech

© 2009 Elsevier Inc. All rights reserved.
Corresponding author: Roy H. Hamilton, MD, MS 3 Gates Building, Hospital of the University of Pennsylvania, 3400 Spruce
Street, Philadelphia, PA 19104 Roy.Hamilton@uphs.upenn.edu phone: 215-779-1603 fax: 215-662-3362 .
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our
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Introduction
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Persistent aphasia is a common and frequently devastating consequence of dominant
hemisphere strokes, for which the effectiveness of clinical interventions is limited (e.g.
Lincoln et al., 1984). Recent evidence suggests that exogenous magnetic and electrical
manipulation of brain activity may facilitate recovery of various faculties after stroke (e.g.
Alonso-Alonso et al., 2007, Schlaug et al., 2008). Repetitive transcranial magnetic
stimulation (rTMS) has yielded encouraging results with respect to motor function (e.g.
Mansur et al., 2005) and neglect (e.g. Brighina, 2003). In patients with chronic nonfluent
aphasia this technique has been used to facilitate long-lasting improvements in naming
ability (Naeser 2005a, 2005b; Martin et al., 2009).

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Most prior studies of rTMS in patients with stroke-related deficits, including aphasia, have
employed inhibitory low frequency (1 Hz) stimulation to the intact hemisphere of the brain.
To date, investigations of the effects of contralesional rTMS on language recovery have
focused on overt naming as the principle measure of performance, and indicate that patients
with chronic nonfluent aphasia who receive 1 Hz rTMS over the posterior pars triangularis
portion of the inferior frontal gyrus (IFG) of the nondominant hemisphere experience
benefits in picture naming that persist for months to years (Naeser et al., 2005a,
2005b;Martin et al., 2009). The frequency of naming deficits in aphasia and the relative ease
of assessing change in naming performance make it a useful measure. However, it remains
unproven whether the benefits in naming that have been observed in response to rTMS
generalize to other abilities that are critical to functional language recovery. In order to
address this issue, we investigated the effect of contralesional rTMS of the right IFG on
tasks that assess elicited propositional speech.

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Impairment of propositional speech is a defining characteristic of non-fluent aphasias, and is
commonly associated with lesions of Broca’s area and underlying deep white matter
structures (Alexander et al., 1990). Picture description is one of the most useful and
frequently employed measures of elicited propositional speech production (Coelho, 2007).
Here we report a subject with a left hemisphere stroke and chronic aphasia who showed
stable deficits of propositional speech over the course of five years prior to our investigation.
Over six sessions, 1Hz rTMS (600 pulses at 90% motor threshold) was administered at six
separate sites in the right frontal lobe (Figure 1a), in order to locate a site that was most
responsive with respect to picture naming. These sites included the region of the motor
cortex corresponding to the mouth, a site on Brodmann Area 44 (BA 44; pars opercularis),
two separate sites on BA 45 (designated as the dorsal posterior and dorsal anterior pars
triangularis), an intermediate site that by some accounts (e.g. Amunts et al., 2004) may
either represent the anterior aspect of BA 44 or the posterior aspect of BA 45 (designated
here as the anterior pars opercularis/ventral posterior pars triangularis; BA 44/45), and a site
on BA 47 (pars orbitalis). Subsequently, 1Hz rTMS (1200 pulses at 90% motor threshold)
was delivered to the identified optimal site for 10 daily sessions over 12 days. Because
rTMS to the intact hemisphere is theorized to improve the function of frontal language
regions, and possibly bilateral temporo-parietal language networks, we predicted that
manipulation of the intact hemisphere at this site would result in persistent improvements in
both naming and propositional speech.

Results
Phase 1: Identification of Optimal Site for Picture Naming
Across the six rTMS sessions there was no effect of session order on picture naming
performance before or after rTMS, for either novel (F[4,9]=0.584; p=0.689) or repeated
(F[4,9]=0.658; p=0.647) items, indicating that there was no effect of practice on
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performance. Repeated stimulus and novel stimulus trials were therefore collapsed during
analysis.

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Two procedures were employed to identify a site at which rTMS improved performance.
First, to evaluate whether the effect of rTMS at each target site differed from its effect at
other sites, one-sample t-tests were performed comparing the difference between pre-TMS
and post-TMS performance (designated the Δ Naming score) at each site to the mean of the
Δ Naming scores for the remaining sites (e.g. Δ Naming for BA 44 was compared to the
mean of Δ Naming for all sites except BA 44; M1 Δ Naming was compared to Δ Naming for
all sites except M1, etc.). Stimulation of the dorsal posterior BA 45 (DP45) was associated
with a significantly greater increase in naming performance compared to the mean change in
performance at all other sites (t[4]=−3.628, p = 0.022), while stimulation of anterior BA 44/
ventral posterior BA 45 (BA 44/45) was associated with a significant decrease in naming
performance (t[4]=−5.823, p = 0.004) (Figure 1b).

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Second, to evaluate whether the change in naming performance induced by rTMS was
attributable to day-to-day variability we calculated the mean variability for the six pre-TMS
sessions; the standard deviation for the six pre-TMS sessions was 3.27. We reasoned that,
for any given site, an improvement in naming that exceeded the pre-TMS score for that site
by more than ±2.5 SDs was not likely to be attributable to chance. The only site at which the
improvement with TMS met this criterion was the dorsal posterior aspect of BA 45 (Figure
2b). In light of the converging evidence from these analyses, this site was thus selected for
Phase 2 of the investigation.
Phase 2: Response to rTMS at Optimal Site
Western Aphasia Battery—The patient’s performance on the Spontaneous Speech
subtest of the WAB was stable over the course of the five years prior to his participation
(Figure 2a). Ten months after administration of rTMS the score on this subtest improved
significantly (one-sample t-test: t[2]=−5.5, p=0.032). This improvement on the composite
subtest was comprised of improvements on both information content and fluency scales.
These numeric changes represented substantive improvements in the patient’s propositional
speech as observed by examiners. For instance, an increase from seven to nine on the
information content scale equated to a change in performance from “mention of at least 6
items in the picture” to “an almost complete description of the picture” in which “at least 10
people, actions, or objects” were named. Similarly, an increase from four to five on the
fluency scale represented a change from “halting, telegraphic speech” with “mostly single
words” to “often telegraphic but more fluent speech with some grammatical organization.”

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Cookie Theft Picture Description—A one-sample t-test comparing the mean number of
narrative words employed to describe the Cookie Theft Picture before and after treatment
with TMS was significant (t[2]=4.453, p=0.045), indicating more narrative words employed
after stimulation than before (Figure 2b). A one-sample t-test comparing the mean number
of different nouns uttered by the patient after receiving rTMS to his pre-TMS baseline was
also significant (t[2]=6.000, p=0.027), indicating that more objects in the scene were
described after stimulation than beforehand (Figure 2c). A one-way ANOVA in which mean
sentence length was the dependent variable and session (baseline, 2 months, 6 months, and
10 months) was the independent variable demonstrated a significant effect of session
(F[3,13]=5.519, p=0.017), indicating a significant increase in sentence length over time
(Figure 2d). A subsequent post hoc t-test revealed a significant increase in mean sentence
length between baseline and 10 months (t[5]=−3.972; p=0.011). Other comparisons of
sentence length between timepoints were not significant. As a way to further quantify the
complexity of the patient’s utterances, a t-test was used to compare the number of closed

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class words (the class of words that includes determiners, conjunctions, pronouns, and
prepositions) used by the patient per sentence before rTMS to his use of these words after
receiving rTMS, collapsed across post-TMS timepoints. This comparison revealed a trend
toward significance (t[11]=−2.152; p=0.054; Figure 2e). Table 1 shows examples of the
patient’s elicited speech on the Cookie Theft Picture description before and after receiving
TMS.
Naming—Compared to performance at baseline, the patient’s performance on naming of
animals, actions and tools, improved between baseline and 6-month follow-up (Figure 2f). A
chi-square test used to compare performance in each category at baseline to 6-month followup revealed a statistically significant improvement (χ2=4.444; p=0.035) for naming of
actions, increasing from 5 of 12 items named to 10 of 12 items. The numerical improvement
in naming of animals (5 items to 6) and actions (7 items to 9), did not achieve statistical
significance.

Discussion

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In a subject with stroke and chronic aphasia, low frequency inhibitory rTMS was applied to
several locations in the contralesional right hemisphere. Stimulation of a single site in the
right IFG resulted in significant improvement in naming. After extended administration of
low-frequency rTMS to that site, the subject showed sustained improvement, not only in
naming, but also in elicited speech, as assessed by his ability to describe visual scenes.
Importantly, the subject’s performance on measures of elicited propositional speech had
been stable for years prior to undergoing rTMS. Consistent with our observations, both the
patient and his wife also thought that there had been a clear but modest improvement in his
speech output and willingness to speak. Our findings support a growing body of evidence
that indicates that inhibition of the intact contralesional pars triangularis results in improved
naming in patients with chronic nonfluent aphasia. Importantly, our findings also extend
prior investigations by demonstrating that improvements in language following
contralesional stimulation may generalize beyond naming to other abilities such as
propositional speech.

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Much of the evidence demonstrating that contralesional rTMS can be used to enhance
language recovery has been reported by Naeser and colleagues. These investigators initially
observed a significant but transient increase in accuracy and decrease in reaction time for
subjects with stroke and nonfluent aphasia in naming pictures immediately following a
single application of 1Hz rTMS to the right pars triangularis for 10 minutes (2002). Similar
to the current study, Naeser and colleagues subsequently administered 10 20-minute
sessions of 1 Hz rTMS to the right pars triangularis in four subjects (Naeser et al., 2005a).
At two months follow-up, there was a significant improvement on the first 20 items of the
Boston naming Test, the Animal Naming subtest of the BDAE, and the Tools/Implements
measure on the BDAE. At 8 months, all three naming test scores continued to improve
relative to pre-TMS testing, but only Tool/Implements was significant. Improvement was
also observed in number of words per longest phrase length in elicited propositional speech
for two of the patients when tested with the BDAE at 2 months post-rTMS.
A recent study by the same group of investigators (Martin et al., 2009) described two
patients with chronic aphasia who received rTMS, one of whom responded well to
stimulation and one who did not. They proposed that differences in the distribution of stroke
may have accounted for differences in response to rTMS. Other investigators have suggested
that the functional role of the right hemisphere in language recovery may differ between
individuals, possibly accounting for differences in response to rTMS (e.g. Winhuisen et al.,
2007). Martin and colleagues observed that in the patient who experienced improvement of

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naming ability, an increase in sentence length on a picture description test was noted. Our
findings support and extend these findings, demonstrating that the propositional speech
ability of a subject who had suffered from stable deficits over several years improved, not
only in terms sentence length, but also with regard to the number of objects described within
a complex scene and the complexity of the sentences employed.

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One intriguing aspect of the current findings is the topographic specificity of rTMS in
eliciting changes in language performance. Stimulating the dorsal posterior pars triangularis
in our subject resulted in a 41% increase in naming ability. However, stimulation of the
nearby anterior pars opercularis/ventral posterior pars triangularis resulted in a 23% decrease
in naming. Naeser and colleagues also found substantial differences in naming ability based
on small changes in the location of stimulation (c.f., Naeser et al, 2005A). While the
mechanism underlying this topographical specificity of rTMS effects has not been fully
elucidated, our results may have important implications for our understanding of
interhemispheric interactions in patients with stroke. It has previously been proposed that
some of the chronic deficits that accompany lateralized strokes may be related to disruption
of mutually inhibitory inputs between the cerebral hemispheres (Fregni & Pascual-Leone,
2007). According to this model, unilateral injuries—for example a dominant hemisphere
stroke— may lead to a reduction of inhibitory input from the damaged hemisphere onto the
intact hemisphere. This release of inhibition may result in increased inhibitory input from
the contralesional hemisphere on the damaged hemisphere, exacerbating the deficits initially
incurred by the destruction of brain structures. This model has served as the central rationale
for applying inhibitory rTMS to the intact contralesional hemisphere to treat a variety of
symptoms associated with unilateral lesions, including paresis, neglect, and aphasia. Our
finding that dramatic changes in performance are associated with small changes in coil
position in the contralesional hemisphere suggests that a more nuanced model of the neural
representation of language after stroke and of the role of interhemispheric relationships is
needed.
One hypothesis that builds upon the existing model of interhemispheric inhibition is that the
topographic specificity of right hemisphere stimulation may be related to anatomic
distinctions in the left hemisphere for representing language. Evidence suggests that there
are regional differences within the left IFG for processing different linguistic properties,
including syntax, phonology, and semantics (e.g. Démonet et al., 1992, Kapur el al., 1994).
Moreover, it has been shown that administration of rTMS to nearby regions of the left IFG
can dissociate these linguistic elements (Gough et al., 2005). Extending this idea,
administration of rTMS to different regions in the right IFG could result in manipulation of
specific linguistic processes, which may affect object naming ability to varying degrees.

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Another potential explanation for the effects of rTMS in the nondominant hemisphere,
which is not mutually exclusive with other accounts, is the idea that language systems in
patients with chronic aphasia may operate in stable but maladaptive states. By that account,
rTMS may provide and exogenous signal that promotes plastic changes, thereby eroding the
stability of maladaptive states and potentially allowing for the development more efficient
states (c.f. Devlin & Watkins, 2007). While this model is speculative, it accommodates one
aspect of the data that is not readily explained by other hypotheses, the finding that language
function improves over the course of months following rTMS (e.g. Naeser et al 2005a,
2005b, Martin et al., 2009). This improvement may reflect the effects of further
enhancement of connection strengths in these reset networks over time as they are utilized
for language processing (e.g. Spatz, 1996; Bi & Poo, 2001).
The finding that our patient experienced greater improvement in naming of actions relative
to animals or tools also contributes to a growing body of evidence that suggests that the

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prefrontal cortex may play a critical role in action naming. Lesion study evidence points to
an association between action naming impairment and lesions involving the left premotor
and prefrontal areas (Tranel et al., 2001). Moreover, rTMS of the left dorsolateral prefrontal
cortex in nonaphasic individuals has been shown to affect both action naming (Cappa et al.,
2002) and processing of verbs (Cappelletti et al., 2008). The finding that stimulation of the
right pars triangularis results in preferential improvement in action naming in patients with
chronic nonfluent aphasia suggests that connections to the prefrontal cortex of the right
hemisphere may also play a role in mediating action naming in individuals with chronic
injury to the left hemisphere.
Our findings add to the relatively small number of reported cases in which rTMS has been
used to improve chronic aphasia. Because we report results from a single subject, future
investigations are necessary to determine the degree to which our findings can be
generalized to other patients with nonfluent aphasia receiving noninvasive brain stimulation.
Moreover, additional measures would be useful for assessing improvement in other domains
of language and the impact of these changes on daily function. Despite these limitations, our
findings support the claim that noninvasive brain stimulation may improve chronic aphasia
and suggest that not only anomia but other aspects of language as well.

Methods
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Clinical History
The patient is a 61-year-old previously healthy right-handed (Edinburgh Handedness
Inventory Score = +100 = strongly right handed; Oldfield, 1971) man with 18 years of
education who worked as a management consultant prior to his stroke. Seven years prior to
participation in the current investigation (2000), he experienced sudden right hemiplegia and
global aphasia, with severe deficits in fluency and comprehension; he was subsequently
found to have an ischemic stroke encompassing the territory of the left middle cerebral
artery (Figure 3). He exhibited persistent symptoms of right paresis and mild nonfluent
aphasia (~3 word phrase length).
In accord with the Declaration of Helsinki, the patient gave informed consent as approved
by the Institutional Review Boards of both the University of Pennsylvania and the Moss
Rehabilitation Research Institute.
Language Measures

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Propositional Speech—On three separate occasions over the course of five years
preceding his participation in the present investigation (November 2003, February 2005, and
March 2007) the patient’s language ability was evaluated with the Western Aphasia Battery
(WAB) (Shewan & Kertesz, 1980), which includes a subscale for spontaneous speech. This
subscale is comprised of two 10-point measures rating information content and fluency. An
experienced examiner scored these dimensions based on the patient’s ability to answer a
series of six autobiographical questions (e.g. “What is you address?”) and his ability to
describe a complex scene. For the scene description, he was presented with the picture and
asked to describe everything occurring in the scene. Examiner interruptions were kept to a
minimum and limited to general prompting (e.g. “anything else?”). The patient’s speech was
transcribed to facilitate scoring and analysis. He underwent identical follow-up testing with
the WAB 10 months after completing rTMS.
In addition, the patient underwent baseline evaluation for the present study seven years after
his stroke (September 2007). The Cookie Theft Picture Description subtest of the Boston
Diagnostic Aphasia Examination (BDAE 3rd Ed., Goodglass, Kaplan, Baressi, 2001) was

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employed as the principle measure of propositional speech and fluency. As with the WAB
picture description, the patient was presented with the scene and asked to describe
everything occurring in the picture. The Cookie Theft Picture Description was administered
at baseline (September 2007) and at two, six, and ten months following administration of
rTMS. Scoring of performance included measurement of the number of narrative words and
sentences or topic comments used to describe the scene, the mean length of sentences, and
the number of unique nouns, verbs, and closed class words employed.
Naming—The Naming in Categories subtest of the BDAE was administered (Goodglass,
Kaplan, Baressi, 2001). This subtest consists of three categories: Actions, Animals, and
Tools/Implements. Each category consisted of 12 black-and-white line drawing stimuli. The
examiner directed the patient to name the action, animal, or implement depicted. The task
was self-paced. Answers that contained one phonemic error were counted as correct to
account for the patient’s dyspraxia of speech.
Phase 1: Identification of Optimal Site
MRI Methods—MRI data was collected on a 3.0 Tesla Siemens Trio Scanner. Highresolution whole-brain T1 -weighted images were acquired (TR=1620ms, TE=3.87ms,
FOV=192×256 mm, 1×1×1 mm voxels) using a Siemens 8-channel head coil.

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TMS Methods—Stimulation was administered with a Magstim Rapid transcranial
magnetic stimulator, connected to a 70mm diameter figure-of-eight coil (Magstim,
Whitland, UK). The Brainsight system (Rogue Research, Montreal) was used to co-register
MRI data with the location of the subject and coil in both phases of the study. The patient’s
motor threshold was established according to published criteria (Rossini et at, 1994). On six
separate days over the course of two weeks, he received 1Hz stimulation at 90% of motor
threshold for 10 minutes (600 pulses), delivered to six sites on the right IFG (Figure 2a): the
motor cortex (M1), pars opercularis (BA 44), dorsal posterior pars triangularis (DP BA 45),
dorsal anterior pars triangularis (DA BA 45), anterior pars opercularis/ventral posterior pars
triangularis (BA 44/45), and pars orbitalis (BA 47).

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Snodgrass and Vanderwart Items—Prior to and immediately following stimulation at
each candidate site, the patient was shown sets of 40 line drawing stimuli taken from the
Snodgrass and Vanderwart picture database (1980). Each picture was presented with a
laptop computer for 10s and was preceded by a 120 ms tone and a 1s ISI. The patient was
instructed to name the picture as soon as it appeared on the screen. To assess practice
effects, 20 of the 40 items on each list were repeated in each of the twelve testing blocks (six
blocks immediately before rTMS to each of the six candidate sites; six post-TMS blocks),
while the other 20 items in each block were novel. Lists were controlled for frequency and
visual complexity. All words were 1–2 syllables in length. No two sequential words within a
list belonged to the same semantic category or had the same initial phoneme. Responses that
differed from the target word by one phoneme were counted as correct.
Phase 2: Administration of rTMS at Optimal Site and Follow-Up
TMS Methodology—The patient received rTMS for 10 days in a 12-day period (Monday
— Friday, weekend off, Monday – Friday) at the site (dorsal posterior pars triangularis)
shown to produce the greatest improvement in naming. Each session consisted of 1200
pulses at a frequency of 1 Hz at an intensity of 90% of motor threshold.
Follow-Up—The patient underwent follow-up evaluation with the Cookie Theft Picture
Description and BDAE Naming in Special Categories two months and six months after the
10 sessions of rTMS. In addition he completed the spontaneous speech subtest of the
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Western Aphasia Battery and the Cookie Theft Picture Description 10 months after
administration of the rTMS.

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Acknowledgments
We wish to thank Adelyn Brecher and Dr. Marianna Stark for their invaluable assistance in the preparation of this
manuscript.

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Figure 1.

a) The six sites at which TMS was delivered in Phase 1 of the study: M1 corresponding to
the mouth (blue), Brodmann area 44 (BA 44; green), dorsal posterior BA 45 (red), dorsal
anterior BA 44/ventral posterior BA 45 (yellow), dorsal anterior BA 45 (purple), and BA 47
(brown).
Figure 1b) The difference in performance on a naming task before and after rTMS to the six
right hemisphere sites. Hatched lines indicate significant differences.

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Figure 2.

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Performance on measured of propositional speech and naming. 2a) The Western Aphasia
Battery spontaneous speech subscale. Black bars indicate the Information Content
component of the Spontaneous Speech subscale; grey bars indicate the Fluency component.
2b-2e) Performance on the Cookie Theft Picture Description: b) total number of narrative
words used, c) number of different nouns used, d) mean sentence length, and e) number of
closed class words used per sentence. Vertical bars represent standard error. 2f) Performance
on the Naming in Categories subtest of the BDAE. Improvement in action naming between
baseline and six months is significant (asterisk).

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Figure 3.

T1-weighted MRI (1mm slice images with field of view 192 × 256 × 80; axial images
depicted are—from inferior to superior—slices 124, 100, 90, 84, 78, and 66). Extensive
cortical lesion is present in middle and inferior frontal gyrus areas (includes Broca’s area),
and in most of the middle and superior temporal gyrus areas (includes Wernicke’s area).
There is some sparing of deep white matter, adjacent to inferior frontal horn (arrows, medial
subcallosal fasciculus), deep to Broca’s area. Extensive sensorimotor cortex and parietal
lobe lesion is present, with sparing of parts of BA 37 and 39 (angular gyrus).

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Table 1

Cookie Theft Picture Description at Baseline and 6 Months Following TMS

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Baseline

6 Months

this is cookies
kids
chair
almost fall
(unintelligible) almost fall
girls cookies too
this is big girl

food
big man water
holding water cause otherwise rain washing.
guy chairs but not good cause ohhhhh! (pantomimes
falling)
cookies!
far
almost too far, but you know what?
one hand, no, two hands
also girl I like cookies too so
nice
nice outside I think not cold.
girl, big girl washing clean

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