About the presenter: Janis Costello Ingham received her B.S. in Speech Pathology and Audiology from Northwestern University in 1964 and her master's and doctoral degrees in the same discipline from the University of Kansas in 1966 and 1969, respectively. Since that time she has served on the faculty of the Department of Speech and Hearing Sciences at the University of California, Santa Barbara. She holds the Credential of Clinical Competence in Speech-Language and is a Fellow of ASHA and a member of Division 4: Fluency and Fluency Disorders. Her research and teaching have focused on assessment and treatment of stuttering and phonologic disorders, particularly with children. Most recently she has concentrated her research efforts, with her husband, Roger, and colleague Peter Fox, on neurogenic and genetic aspects of stuttering. She has served as editor of the Journal of Speech and Hearing Disorders, as ASHA's Vice President for Research and Technology, and currently as Vice President for Research and Academic Development of the Council of Academic Programs in Communication Sciences and Disorders. | |
About the presenter: Roger Ingham is Professor of Speech and Hearing Sciences at the University of California, Santa Barbara. He was born in Australia and received his B.Sc. and Ph.D. in psychology (1972) from the University of New South Wales in Sydney, Australia. He has published 3 books and more than 150 papers, principally on developmental stuttering. His research has focused on the development of treatments and measures of stuttering, the neurology of stuttering and most recently its genetic basis. He is an ASHA Fellow and has been the recipient of several federally funded research grants for investigating stuttering. He also holds an adjunct appointment with the University of Texas Health Science Center, San Antonio, where, in collaboration with Peter Fox and his wife, Janis Costello Ingham, he has developed a program of research on stuttering using brain imaging techniques including PET, event-related fMRI and transcranial magnetic stimulation. | |
Introduction
The cause of
stuttering has been a question of interest no doubt since the first person who
stuttered spoke aloud to his or her first listener. Professor Bill Perkins, a well-known American scholar of
stuttering, once pointed out that a hallmark of the field of stuttering is that
no theory ever dies – they all live on forever. This could serve as a commentary on the fact that many
theories of the cause and nature of stuttering have not been testable using the
scientific method and so have not been able to be disproved – thus they
linger on.
That something could
be amiss in the neurologic systems of people who stutter - that is, in their
brains, is one of the often-reappearing theories of the cause of
stuttering. One particular area of
interest has been the potential for problems in the auditory system of stutterers,
especially given the fluency-inducing effects of auditory stimulation such as
masking, chorus reading, and delayed auditory feedback.1 (The latter, of course, is now known to
be more likely a by-product of slowed/prolonged speech rather than changes made
to a speaker’s auditory feedback system.) Travis’s2 early theory of inadequate
cerebral lateralization is another example. Although we know now that activity in both sides of the
brain is intimately integrated and coordinated during speech production and
perception, it is also well known that some degree of hemispheric
specialization exists. In
simplistic terms, for the vast majority of people (right handed and left handed) the left side of the brain is relatively
more active during the processing of language; and the right side of the brain
dominates when more global functions, such as spatial perception, are required.3 Variations on the theme of inadequate
cerebral lateralization in people who stutter have suggested that the left
hemisphere may compete with the right for the processing of language, or even
that people who stutter may use exclusively the ill-equipped right side of
their brains to process language.
Until the last decade or so, support for such theories has been derived
from inferential evidence. That
is, scientists have had to rely on indirect measures of brain function such as
electrical activity measured from the scalp during speech perception (not
speech production, because
movement artifacts interfere with the analysis of the signal),4
voice reaction times,5 dichotic listening,6 and finger
tapping.7 Nonetheless,
findings from many of these studies, especially those conducted through
comparisons between performances of adult stutterers and nonstutterers, have
offered support for the view that the brains of people who stutter function
differently for speech production than the brains of those who do not stutter.
The development and
increasing sophistication of various brain imaging technologies have further
enabled researchers to study the brains of people who stutter. Now it is possible to observe brain
activity more directly, in three dimensions throughout the entire brain, and
even during actual speech. The
bulk of the remainder of this paper will concentrate on presenting an overview
of the “San Antonio studies,” – that is, one aspect of the
brain imaging research that we have been conducting since the early ‘90s
with our colleagues at the Research Imaging Center (RIC) of the University of
Texas Health Science Center, San Antonio – led by Peter T. Fox, M.D. and
a diverse core of researchers and technicians whose expertise in brain imaging
techniques, including the analysis of images, has been pioneering. (We are zooming in on our own research
because of space limitations and because, of course, it is the work we know
best. Others are also conducting
research in this arena and some representative publications are contained in
the reading list at the end of this paper, for your reading pleasure.)
Positron Emission
Tomography (PET)
We began our brain imaging research program by
utilizing positron emission tomography (PET) to identify cerebral regions
related to the occurrence of stuttering.
This procedure is commonly referred to as functional brain imaging. In a
typical PET study the research subject lays face-up on a flat platform with his
or her head held firmly in place inside the PET camera, which encircles the
head. It is necessary to prevent
head movement because in each condition of an experiment multiple scans of the
brain are acquired and these several “pictures” are averaged
together to produce the findings for that condition. Immediately prior to each scan, the patient is injected
(through a line into a vein in the arm) with a small dose of radioactive water
(H215O).
When the radioactive material reaches the brain (less than 15 seconds
following injection) the PET camera registers relative cerebral blood flow
(CBF) throughout the brain.
Previous research has demonstrated that blood flow increases in regions of the brain that are relatively more
active during a given task and decreases in those that are relatively less active during that task. In our
research, each scan lasts 40 seconds and scans are taken about 10 minutes
apart, which provides sufficient time between scans for the radioactive tracer
to dissipate and wash through the person’s system. The findings of each subject’s
scans are overlaid onto an anatomical MRI (magnetic resonance image) of that
person’s brain and then those data sets are combined across subjects to produce
a single data set averaged across all subjects in the group (e.g., stutterers
or nonstutterers). The
computer-processed data on which we rely are in two forms. One, we look at the overlays that
display a group’s relative cerebral blood flow in different regions of the
brain. These are the well-known
colorful images of brain activity that indicate, by the use of a color scale,
areas of the brain with relatively intense blood flow, usually colored bright
red or yellow, through to regions of apparent deactivation (relative to the
brain activity at rest), which are displayed in greens. When regional CBF is viewed in this
manner, the images are typically presented in the horizontal view as a series
of individual 4-6 mm thick “slices” of the brain (from the top of
the head through to the brain stem, as though one were looking down on the
brain from the top). (See the
images presented on page 10.)
A more refined analysis of the images is obtained from
computer-based statistical analyses of changes in the regional tissue uptake of
the H215O.
This is accomplished through “subtraction analyses” wherein
CBF levels from scans obtained when the brain is at rest (subject lying still
with eyes closed) are subtracted from CBF levels during activations generated
by specific experimental conditions.
These calculations produce a list of pinpointed locations in the brain
where levels of CBF are statistically significantly higher or lower than the
brain’s CBF at rest. These
locations are described as clusters of voxels (voxel = 2x2x2 mm area) present at identified coordinates in Talairach space,8 where x = the right-left dimension, y = the anterior-posterior
(front-back) dimension, and z = the superior-inferior (high-low) dimension. This “mapping” of locations in the brain
activated (or deactivated) by particular, carefully selected tasks, is
fundamental to functional brain imaging techniques and has led to now abundant
information regarding regions of the brain associated with normally produced
speech (mostly based on single word responses).9,10 For example, if one had a Talairach and
Tournoux “map” handy,
one could see that a cluster of voxels significantly activated at x = -46, y = -10, z = 40 by a group of control subjects reading aloud means that this
spot in the precentral gyrus of the frontal lobe, which represents mouth
movement, is activated by oral reading.
Given this somewhat over-simplified tutorial on PET brain imaging, let’s review the
findings that this procedure has produced from our work with adult males and
females who stutter. One of
the early questions we asked was whether the brains of stutterers and
nonstutterers are different when they are not speaking, that is, when their brains are “at
rest.”11 We
compared the resting-state CBF of 10 adult men who were chronic developmental
stutterers and 19 age-matched men who did not stutter. All were right handed and all received 3 resting-state
scans. Comparisons were made
across 37 regions in each hemisphere, encompassing essentially the entire
brain. No significant differences
between stutterers and nonstutterers were found. This demonstrates that, in terms of CBF at least, there are
no fundamental differences in stutterers’ and nonstutterers’
brains. If such differences exist,
it seems they would have to be associated with how the brain functions during
speech production.
Data regarding the latter hypothesis were obtained in
another study.12 PET
scans obtained from 10 male adult left handed stutterers were compared to scans
from 10 age- and sex-matched left handed normally fluent controls. Subjects received 3 scans in each of 3
conditions: reading aloud (during
which all of the stutterers stuttered), reading in chorus with another speaker
(during which none of the stutterers stuttered), and eyes-closed rest (for
subtraction purposes). Stuttering
was associated with patterns of brain activity in particular regions that were
highly different from controls, primarily in the motor system, as follows: M1 (brain region for mouth movements)
was right- rather than left- lateralized; SMA (supplementary motor area, at the
top of the brain) was more broadly and intensely activated; lateral Brodman
Area (BA) 6 (superior lateral premotor cortex) was strongly activated on the
right (and barely activated at all by the controls); and cerebellar activations
more than doubled the extent observed in controls. Stutterers alone activated several regions: bilateral
insula, and left claustrum, thalamus, and globus pallidus. Another important finding was that only
stuttering was associated with deactivation in the auditory areas of the superior and posterior
temporal lobe. When patterns of
CBF during stuttering were compared with the fluency induced by chorus reading,
brain activity of the stutterers approached the patterns observed in the controls,
but the stutterers’ neural systems did not completely normalize.
As we all recognize, when people who stutter read or
speak, not all syllables are stuttered.
Therefore, in the study described above, the production of both
stuttered and nonstuttered syllables occurred in the “stuttering
condition;” therefore, the cerebral regions activated (or deactivated)
during this condition were the product of both stuttered and nonstuttered
behaviors. In order to refine the
above analysis so that cerebral areas associated with stuttered and
nonstuttered speech could be differentiated, a follow-up project13
using the data from the above-described study was conducted. A performance-correlation analysis was
performed, based on the principle that the intensity of brain activations is
highly correlated with the frequency of the behaviors they generate. In this case, regions of brain
activation/deactivation that were correlated with the frequency of stuttering
and the frequency of syllable production (essentially, fluent speech) were
separately identified. This more
sensitive analysis still turned up the same findings: that stuttering is associated with overactivity of the right cerebral regions associated primarily with speech planning and
execution, and with underactivity of auditory regions within the temporal lobe. In addition, nonstuttered speech in
these male stutterers is associated with left-sided overactivity in
cerebellum. (Lateralization in
cerebellum is typically opposite to that of the cerebrum).
A logical interpretation of the findings from these
studies is that stuttering appears to stem from a neurologic system that has
weaknesses in regard to (1) the selection and organization of the speech motor
plan and (2) the use of the auditory system for self-monitoring of one’s
speech.
One drawback of these studies is that the experimental
design doesn’t allow one to determine if the aberrant areas of cerebral
activity are responsible for the
stuttered speech production or if they are a side effect of the extra and unusual motor behaviors that occur
when a person is stuttering - the old “chicken and egg”
problem. To investigate this issue
we enlisted 4 stutterers and 4 controls who had participated in the previously
described PET study.14
They were asked, in one condition, silently to read a passage and imagine
that they were stuttering, and in
another condition silently to read the passage while simultaneously hearing it
read by another person (the chorus reading stimulus) and imagine that they
were reading fluently. (A third condition was eyes-closed
rest, for subtraction purposes.)
For the most part, regional activations and deactivations associated
with imagined stuttering overlapped those associated with actual stuttering,
including deactivations in the auditory system. A prominent, and logical, exception was activation of M1
(mouth movement), which did not occur prominently in the imagine
condition. These findings indicate
that overt stuttering is not a prerequisite for the prominent regional
activations and deactivations associated with stuttering. Thus these unusual activations must not
be merely a byproduct of the movements of stuttering but a fundamental
component of the creation of a moment of stuttering.
There’s one more PET study in our current
arsenal that is of particular interest because it compares brain imaging
findings between men and women stutterers (and controls).15 Little research aimed exclusively at
female stutterers exists, and no other in brain imaging, although differences
in brain structure and function between men and women in the general population
have been documented.16,17
In this study we precisely replicated the oral reading-chorus reading
paradigm and performance-correlation analysis described for our previous study
with 10 female right handed developmental stutterers and a matched group of
controls. Their findings were
compared to the results for males reported above. Indeed, there were differences, and similarities, between
male and female stutterers in terms of brain regions that were exclusively
associated with the presence of stuttered speech. The similarities, which one might assume are the aberrant
activations/deactivations critical to stuttering because they are present in
both genders, are: anterior
insula, which is highly active during stuttered speech (also shown by to be
defective in adults with apraxia18); the auditory association area
of the temporal lobe (BA 21/22), which is essentially inactive during
stuttering and which we theorize plays a role in self-monitoring; and
Broca’s area (BA 44/45), which was also deactivated during stuttering
– an additional finding gleaned from the more sensitive analyses carried
out with these data. Broca’s
area is well known to participate in normal speech motor planning and
production.19 Even in
these three areas, however, the men and women stutterers differed: females showed bilateral
activation/deactivation, while the males’ patterns were unilateral (right
sided for anterior insula and the temporal lobe, left sided for Broca’s
area). The images on the following
page illustrate some of these findings.
They are horizontal slices that cross the temporal lobe at about the
level of the ears (z = 6).
Gender-based differences for the females occurred
primarily in activations during stuttering in the basal ganglia; for males, a
major difference was seen in the prominence of cerebellar activations.
The exact meaning of all these findings continues to
be illusive, especially because we do not yet completely understand the neural
linkages among the areas that have been identified as playing a part in
stuttering, or how these areas interact with cerebral regions that produce
speech in general. From our
findings we have learned, however, that the brains of people who stutter are
indeed different from the brains of those who do not and that those differences
appear to be confined to the functions of speech-motor planning (and, perhaps,
production) and internalized auditory feedback. Whether these differences are present at the genesis of
stuttering, or are the byproducts of our adult subjects’ years of
stuttering practice, awaits imaging studies with children, which are on the
horizon.
Some
Words of Caution in Regard to PET Technology
Although
PET methodology has offered landmark opportunities for researchers to observe
the brain in action, there are certain drawbacks inherent in the current
technology. First, we typically
must study groups of patients, rather than individuals – although the
design of more powerful PET cameras will soon alleviate this problem. Second, although PET has superior
spatial resolution (that is, we can pretty accurately identify where in the brain activity associated with a given task is
occurring), it does not offer sensitive temporal resolution.
This is exemplified in our research wherein we study stuttered speech in
40-s periods of oral speaking that contain individual moments of stuttering
embedded in sequences of nonstuttered syllables. (Debate exists, of course, regarding whether the
“nonstuttered” syllables of stutterers are “normal” or
also aberrant in ways that are not necessarily perceptually notable.20 In fact, some brain imaging studies of
stutterers’ speech have not attempted to control for the presence or absence
of stuttering.) Nonetheless, PET
does not permit the analysis of a particular moment of speech, such as a moment
of stuttering. Brain activity for
the entire 40 seconds is imaged.
Therefore, comparisons between stuttered and nonstuttered speech are
less definitive because the stuttered sample also includes nonstuttered
syllables (hence our use of performance-correlation analyses). We are currently doing pilot work with
event-related fMRI that may solve this obstacle. Third, the ability of the subtraction design to segregate
brain activity related exclusively to a particular behavior or cognitive
activity has been questioned.21 A fourth, very serious shortcoming of the PET methodology is
that it is not, indeed, a “standardized” methodology. Therefore, our ability to make
meaningful comparisons among results of different brain imaging studies of
stuttering is negatively impacted when studies differ in the (a)
speaking/nonspeaking tasks imaged, (b) statistical analysis packages utilized,
(c) brand of PET camera used, or particular PET technology used, and (d) subjects’ age, gender and
perhaps severity of stuttering.
Brain imaging research in stuttering is still a fresh, young area of
research, and as more studies are conducted, results from disparate studies
will begin to converge and pinpoint findings that consistently occur for
stuttering. Some of that
convergence occurs now, but one has to search for it!
Clinical
Implications of Brain Imaging Findings
At
this point in the short history of brain imaging research in stuttering, the
clinical significance of the findings is untested. For many stutterers, certainly the knowledge that their
stuttering most likely has a neurological foundation is of value. For some, it seems to confirm their
personal experience with their disorder.
In addition, the use of imaging to compare patterns of brain activity
prior to and following successful treatment will inform clinicians and
researchers about the kinds of changes that are necessary to produce and maintain
fluency. (We have recently begun
studies with untreated, recovered stutterers in order to gauge the nature of
neurologic change necessary to produce fluency.) Imagining research will have clinical relevance if it
eventually facilitates our capabilities in regard to recognizing consistent
neural patterns that can differentiate between children whose stuttering will
or will not persistent. And
lastly and importantly, imaging might eventually be used to identify an
individual’s stuttering speaker’s aberrant neural system(s) and
thereby the clinician in tailoring treatment to modify that individual’s
aberrant system. So, although
scientists are still at the early stages of basic imaging research in stuttering,
the clinical potential seems immense.
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Additional Readings on Brain Imaging and Stuttering