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Stuttering and the Basal Ganglia 1
Running head: STUTTERING AND THE BASAL GANGLIA
Stuttering and the Basal Ganglia Circuits:
A Critical Review of Possible Relations
Per A. Alm
Department of Clinical Neuroscience and Department of Psychology,
Lund University, Sweden
Published in: Journal of Communication Disorders,
2004, vol. 37, 325-369.
https://doi.org/10.1016/j.jcomdis.2004.03.001
E-mail: Per.Alm@psykiatr.lu.se
Abstract
The possible relation between stuttering and the basal ganglia is
discussed. Important clues to the pathophysiology of stuttering are given
by conditions known to alleviate dysfluency, like the rhythm effect,
chorus speech, and singing. Information regarding pharmacologic trials,
lesion studies, brain imaging, genetics, and developmental changes of
the nervous system is reviewed. The symptoms of stuttering are
compared with basal ganglia motor disorders like Parkinson's disease
and dystonia. It is proposed that the basal ganglia-thalamocortical motor
circuits through the putamen are likely to play a key role in stuttering.
The core dysfunction in stuttering is suggested to be impaired ability of
the basal ganglia to produce timing cues for the initiation of the next
motor segment in speech. Similarities between stuttering and dystonia
are indicated, and possible relations to the dopamine system are
discussed, as well as the interaction between the cerebral cortex and the
basal ganglia. Behavioral and pharmacologic information suggests the
existence of subtypes of stuttering. LEARNING OUTCOMES: As a
result of this activity, the reader will (1) become familiar with the
research regarding the basal ganglia system relating to speech motor
control; (2) become familiar with the research on stuttering with
indications of basal ganglia involvement; and (3) be able to discuss basal
ganglia mechanisms with relevance for theory of stuttering.
Keywords: Stuttering, Basal ganglia, Dopamine, Dystonia, Cluttering
Stuttering and the Basal Ganglia 2
Table of Contents
Abstract ......................................................................................................... 1
1. Introduction .............................................................................................. 3
2. Overview of the basal ganglia anatomy and functions ............................. 3
3. The rhythm effect, motor control, and timing .......................................... 5
3.1. The rhythm effect ............................................................................. 5
3.2. Internally versus externally cued movements................................... 5
3.3. Chorus speech ................................................................................... 5
3.4 Song ................................................................................................... 6
3.5. The effect of increased attention ...................................................... 6
3.6. Basal ganglia timing cues ................................................................. 6
4. "Neurogenic" stuttering ............................................................................ 8
4.1. The relation between "neurogenic" and "developmental" stuttering 8
4.2. Localization of lesions in neurogenic stuttering ............................... 8
4.3. The putamen is influenced by the CM nucleus in the thalamus ....... 9
4.4. Summary........................................................................................... 9
5. Imaging of brain activation in stuttering................................................... 9
5.1. Abnormalities in the basal ganglia? ................................................ 10
5.2. Activation compensating for deficient speech automaticity? ......... 10
5.3. Lateralization and stuttering ........................................................... 11
6. Stuttering and dopamine ......................................................................... 11
6.1. Dopaminergic drugs and stuttering ................................................. 11
6.2. Stuttering and FDOPA-PET ........................................................... 13
6.3. Temperament and motor activity .................................................... 13
6.4. Stuttering and ADHD ..................................................................... 14
6.5. Is stuttering a motor stereotypy? .................................................... 14
6.6. Stuttering, emotions, and learning .................................................. 15
7. Stuttering and dystonia ........................................................................... 16
7.1. Introduction .................................................................................... 16
7.2. Dystonia and the basal ganglia ........................................................ 16
7.3 Dystonia and dopamine .................................................................... 17
7.4. Task-specificity ............................................................................... 17
7.5. Fast sequential movements—expansion of cortical maps and
increased gain ......................................................................................... 17
7.6. Sensory effects in dystonia and stuttering ....................................... 18
7.7. Arguments against similarity between stuttering and dystonia ....... 19
7.8. Summary, dystonia and stuttering ................................................... 20
8. Negative and positive symptoms of stuttering ........................................ 20
9. Cerebral development, aging, and degeneration ..................................... 21
9.1. Age of onset, recovery, and gender ratio ........................................ 21
9.2. Aging and stuttering ........................................................................ 22
9.3. Stuttering and cerebral degeneration or lesions .............................. 22
9.4. Summary of development and stuttering ........................................ 22
9.5. Developmental changes of the nervous system .............................. 22
10. Anomalies of the cerebral cortex and possible relations to the basal
ganglia ......................................................................................................... 25
10.1. Increased area of planum temporale ............................................. 25
10.2. Increased gyrification .................................................................... 25
10.3. Somatosensory white matter disturbance ...................................... 26
11. Conclusions ........................................................................................... 26
Acknowledgements ..................................................................................... 27
Appendix A. Continuing education ............................................................. 28
References ................................................................................................... 29
Stuttering and the Basal Ganglia 3
Stuttering and the Basal Ganglia Circuits:
A Critical Review of Possible Relations
1. Introduction
Research concerning the nature of stuttering has produced an
extensive amount of data during the past century, but the mechanisms
behind the speech disruptions and the speech initiation problems are still
not clear. An intriguing aspect of stuttering is the various conditions
which can temporarily alleviate dysfluency in most cases: the rhythm
effect (speaking to the pace of a metronome), singing, chorus speech,
and altered auditory feedback (Wingate, 2002). The often dramatic
improvements in fluency caused by these conditions indicate that
stuttering is not the result of some general speech motor instability,
instead there seem to be specific causal mechanisms leading to the
speech problems.
In this article possible relationships between stuttering and the
functions of the basal ganglia (BG) circuits are reviewed and discussed.
This review leads to the proposal that the circuits through the basal
ganglia play a key role in the mechanisms of stuttering.
The BG are the largest subcortical structures in the human
forebrain, and they are placed in a key position to influence motor
behavior, emotions, and cognition (Graybiel, 2000). The idea that
stuttering may be related to the BG is not new. As early as 1934 Seeman
suggested that stuttering is the result of disturbed BG function (as cited
in Van Riper, 1982). More recent suggestions for BG involvement in
stuttering come from Rosenberger (1980), Caruso (1991), Wu et al.
(1995), Lebrun (1998), and Victor and Ropper (2001), and others.
First an overview of the basal ganglia anatomy and functions will
be presented. Thereafter several aspects of basal ganglia functions and
disorders will be discussed in relation to stuttering: motor control and
timing, lesions, brain imaging, dopamine, emotional influences,
developmental changes of the BG, and similarities between stuttering
and disorders like Parkinson's disease and dystonia. The BG operate in a
close relation with the cerebral cortex, and therefore some important
findings about the cortex and stuttering will also be discussed, from the
perspective of the basal ganglia functions. Lastly tentative conclusions
will be presented. Among the suggested conclusions can be mentioned
that the core dysfunction in stuttering is proposed to be impaired ability
of the basal ganglia to produce timing cues, that developmental changes
of dopamine receptor density in the putamen might explain the frequent
pattern of early childhood onset and recovery of stuttering, and that
stuttering is likely to be a heterogeneous disorder with subtypes showing
different responses to different types of dopaminergic medication.
2. Overview of the basal ganglia anatomy and functions
Even though the understanding of the BG circuits still must be
considered as highly incomplete, knowledge has grown rapidly during
the last decades. The model presented here is simplified, mainly limited
to the aspects most relevant to the discussion. (For more thorough
reviews, see for example Mink (1996) and Victor and Ropper (2001).)
The basal ganglia consist of a set of interconnected subcortical
nuclei. The main input nucleus is the striatum, which receives
topographical excitatory projections from almost the entire cerebral
cortex, especially from the sensorimotor and frontal cortex (Parent,
1996). The striatum and the downstream structures in the basal ganglia
are organized in topographically and functionally segregated pathways.
The cortical inputs to the striatum are convergent, for example in such a
way that sensory and motor cortex areas converge into single striatal
zones (Flaherty & Graybiel, 1991).
The striatum is located close to the globus pallidus, which is
divided into an external (GPe) and an internal part (GPi) (DeLong,
2000). The GPi is one of the main output nuclei1 of the BG, and it
projects, via various nuclei in the thalamus, to most cortical areas of the
frontal lobe (Alexander, Crutcher, & DeLong, 1990). This architecture
means that the BG is part of extensive loops, basal ganglia-
1 The output structures of the basal ganglia are the GPi and the
substantia nigra pars reticulata (SNr), which have similar neurons and
similar connections. In monkey it has been shown that the bulk of the
output from the putamen passes through GPi, while the most of the
pathways from the caudate nucleus pass through the SNr (Mink, 1996).
In order to simplify the discussion will both GPi and SNr be referred to
as GPi.
Stuttering and the Basal Ganglia 4
thalamocortical circuits, which link almost the entire cortex to the
cortex of the frontal lobe. The GPi also has descending output to the
brain stem. Through this pathway the BG can influence brain stem
functions like inhibition of auditory input (Swerdlow & Geyer, 1999). In
summary, the BG modulate the activity of the frontal cortex and the
activity of parts of the brain stem.
The striatum can be divided into three main parts: (a) the
putamen, (b) the caudate nucleus, and (c) the ventral striatum. This
division roughly corresponds to a functional division of the basal
ganglia-thalamocortical circuits: (a) (sensori)motor circuits of the
putamen, with output to the primary motor cortex, the supplementary
motor area (SMA), and the premotor cortex; (b) associative circuits of
the caudate nucleus, with output to the prefrontal cortex; and (c) limbic
circuits of the ventral striatum, with output to the anterior cingulate
cortex and medial prefrontal cortex (Parent, 1996; DeLong, 2000). The
ventral (limbic) striatum also receives input from limbic structures, such
as the amygdala and hippocampus (Joel & Weiner, 2000).
The striatum projects to the GPi by two pathways, the direct and
the indirect, see Figure 1. The indirect pathway also includes the
subthalamic nucleus (STN). All projections from the striatum, the GPe,
and the GPi are inhibitory, while the projections from the cortex, the
STN and the thalamus are excitatory. The GPi is tonically active,
thereby suppressing thalamic activity. Activation of the direct pathway
inhibits neuons in the GPi, which in turn disinhibits thalamic neurons,
finally resulting in excitation of cortical neurons. Activation of the
indirect pathway has the opposite effect, activating the GPi and thereby
inhibiting the cortex. (DeLong, 2000) In this way the two pathways
balance each other, modulating cortical activity.
Mink and Thach (1993) suggested a model where the indirect
pathway provides a diffuse background inhibition of behavioral
impulses, while the direct pathway gives a focused activation of the
desired behavioral program. In this model the basal ganglia play an
important role in inhibiting potentially competing motor programs. This
may be a general mechanism for action selection where "the winner
takes all", by facilitation of the strongest cortical signal and suppression
of the rest (Kropotov & Etlinger, 1999). In other words, a mechanism
for increasing the signal-to-noise ratio in both the motor and the
cognitive system.
Thal
STN
GPi
GPe
Striatum
D2 D1
Cortex
Direct
Indirect
+
-
SNc
Figure 1. Simplified diagram of basal ganglia-thalamocortical circuitry
(motor circuit). White arrows are excitatory, black are inhibitory. GPe =
external segment of globus pallidus; GPi = internal segment of globus
pallidus; STN = subthalamic nucleus; SNc = substantia nigra pars compacta;
Thal = thalamus. The striatum projects to the GPi by a direct and an indirect
pathway. The activity in these pathways is modulated by dopamine from the
SNc: D1-receptors activate the striatal neurons forming the direct pathway
while D2 receptors inhibit the striatal neurons in the indirect pathway.
Adapted from Mink and Thach (1993), Graybiel (2000), and DeLong,
(2000).
-------------------------------------------------------
A key role in the basal ganglia is played by the dopamine
projections from the substantia nigra pars compacta (SNc) to the
striatum, modulating the activity of striatal neurons in a complex way.
According to a simplified model the striatal neurons forming the direct
pathway mainly have excitatory D1-receptors, while the striatal neurons
in the indirect pathway mainly have inhibitory D2-receptors. This means
that increased release of dopamine would facilitate behavioral activation
through the direct pathway. At the same time would increased release of
dopamine inhibit the striatal neurons forming the indirect pathway,
resulting in loss of background inhibition of behavioral activity. In brief,
an excessive release of dopamine would lead to general disinhibition of
Stuttering and the Basal Ganglia 5
motor and other behavioral impulses. On the other hand, insufficient
release of dopamine would lead to a general inhibition of movements
and impulses. A well regulated level of dopamine is therefore essential
for the proper functioning of the basal ganglia circuits.
Dopamine also seems to be involved in basal ganglia learning
processes, by strengthening or weakening the efficacy of corticostriatal
synapses (Mink, 1996; Reynolds, Hyland, & Wickens, 2001). In this
way the striatum may learn to respond in certain ways to certain patterns
of cortical activation.
3. The rhythm effect, motor control, and timing
3.1. The rhythm effect
Execution of a complex motor sequence requires control of two
main aspects: the spatial pattern of muscular activation and the exact
timing of each submovement. One of the most effective ways for
persons who stutter to instantly create fluency is to speak to the pace of
a metronome, the so-called rhythm effect. This effect is reported to be
independent of speech rate, with marked reduction of stuttering even at
high speeds like 184 beats per minute (Van Riper, 1982). The rhythmic
stimuli provide external cues for the timing of each syllable. This
phenomenon has a direct parallel in persons with Parkinson's disease, a
disorder of basal ganglia functions due to reduced release of dopamine.
In Parkinson's disease the ability to perform movement sequences is
greatly improved by auditory or visual cues (Georgiou et al., 1993;
Glickstein & Stein, 1991).
3.2. Internally versus externally cued movements
The difference between externally and internally cued movements
is an important theme in motor control research (see for example
Jenkins, Jahanshahi, Jueptner, Passingham, and Brooks (2000)). Several
studies indicate a dominant role of the SMA in internally cued
movements, while the lateral premotor cortex (preMC) seems to play a
key role in externally cued movements (Cunnington, Bradshaw, &
Iansek, 1996). These two motor areas receive their main subcortical
input from different sources: the SMA from the basal ganglia, and the
preMC from the cerebellum (Strick, 1985). In Parkinson's disease the
basal ganglia-SMA system is dysfunctional, while the cerebellar-preMC
system seems to be preserved (Haslinger et al., 2001). Additional
support for this location of functions comes from experimental lesions in
monkeys. Impaired ability for self-initiated movements but preserved
ability for externally cued movements have been observed after bilateral
lesions of the putamen (Nixon & Passingham, 1998), the medial SMA,
or the anterior cingulate cortex (Thaler, Chen, Nixon, Stern, &
Passingham, 1995). Lesions of the preMC did not result in this type of
impairment (Thaler et al., 1995). Investigation of externally cued
movements in Parkinson's disease suggests that the external cues
facilitate movements through the cerebellar-preMC system (Hanakawa,
Fukuyama, Katsumi, Honda, & Shibasaki, 1999), thereby bypassing the
dysfunctional basal ganglia (Glickstein & Stein, 1991) and the SMA
(Cunnington, Iansek, Bradshaw, & Phillips, 1995). This is supported by
a study of Penhune, Zattore, and Evans (1998) indicating that the
cerebellum plays an important role in extracting temporal information
from sensory stimuli.
Cunnington et al. (1996) suggested that the SMA is especially
involved in self-initiated, well-learned, complex, and sequential
movements, and that the functions of the SMA are more closely related
to the timing of movements than to the spatial programming. These
types of function suggest an important role for the SMA in speech.
Furthermore, Cunnington et al. proposed that the basal ganglia, via the
SMA, provide internal timing cues to facilitate the initiation of the
submovements in a well-learned motor sequence. This model presents a
possible mechanism for the rhythm effect in stuttering: that external
timing cues compensate for deficient internal cues from the basal
ganglia to the SMA. The idea that stuttering is a disorder of motor
timing is not new. It was the core in the reasoning of Van Riper (1982),
and this line has been continued by Kent (1984), Caruso (1991), and
others.
3.3. Chorus speech
Most persons who stutter show no dysfluencies when reading in
unison with somebody else (Van Riper, 1982). It seems likely that the
mechanism behind this effect is similar to the rhythm effect. In chorus
reading the voice of the other person provides external timing cues, a
Stuttering and the Basal Ganglia 6
timing pattern that is possible to follow.
3.4 Song
Also singing creates instant fluency in most stuttering persons
(Van Riper, 1982). Singing is the production of musical tones by means
of the voice (Encyclopædia Britannica, 2003b). Music consists of
several elements, but the one indispensable element in all music is
rhythm; melody can not exist without rhythm (Encyclopædia Britannica,
2003a). Rhythm, in music, is the placement of sounds in time
(Encyclopædia Britannica, 2003a). A conclusion is that during singing,
the brain got to have an internal representation of the intended timing of
each sound. This is a difference between speech and song: rhythm is not
an indispensable element in speech. As discussed above, when a distinct
rhythm is applied to speech, stuttering usually disappears (the rhythm
effect). It seems reasonable to suppose that during singing, the internal
representation of rhythm provides internal timing cues for the initiation
of each syllable in a similar way as a metronome provides external
timing cues. If this assumption is correct, the dramatic effect of singing
to eliminate stuttering in most persons who stutter can be viewed as an
indication of dysfunctional timing cues in stuttered speech.
That the mechanisms of cerebral control of singing differ from the
control of speech has been shown by Jeffries, Fritz, and Braun (2003).
Using PET brain imaging these authors compared the pattern of
activation during speech with the pattern during song with words.
Speech resulted mainly in left hemisphere activation, while singing was
accompanied by widespread right hemisphere activation. An interesting
finding was that speech resulted in increased activity in the left dorsal
putamen (the basal ganglia motor circuit) while singing did not result in
such activation of either left or right putamen. This result is well in line
with the suggestion discussed above, that normal speech requires timing
cues from (the left) basal ganglia system, while singing is based on a
different strategy for timing of syllables, mainly involving right
hemisphere structures.
A further indication for a common mechanism behind the effects
of chorus reading and singing comes from the description of
"psychogenic stuttering" by Deal (1982). It was reported that neither
chorus speech nor singing had any effect on the stuttering in this case.
These observations suggest the existence of stuttering-like syndromes
with different causal mechanisms.
3.5. The effect of increased attention
Persons with stuttering are often able to speak fluently for a while
if they change to a non-automatic way of speaking, like imitating a
foreign accent or acting in a role (Bloodstein, 1995). In a similar way,
persons with Parkinson's disease can achieve improved motor ability
without external cues, merely by being instructed to consciously attend
to a particular aspect of the movement (Cunnington, Iansek, &
Bradshaw, 1999). An interpretation of these observations is that
structures outside the basal ganglia system, for example the preMC,
have the ability to provide internal timing cues for movement sequences,
but only during de-automatization of the movements.
3.6. Basal ganglia timing cues
3.6.1. Timing cues from the GP to the SMA
Studies of monkeys have shown that neurons in different parts of
the globus pallidus (GP) signal just before the end of a submovement in
a well-learned and predictable motor sequence. It has been proposed that
this signal is an internal cue that is generated by the basal ganglia to
mark the end of a component in a movement sequence. This signal
would be appropriate to serve as a trigger for the SMA to switch to the
next movement in the sequence (Brotchie, Iansek, & Horne, 1991;
Mushiake & Strick, 1995). According to this model is the first segment
of a movement sequence initiated by structures outside the basal ganglia
(for example by the motor cortex). Then the basal ganglia provide cues
for the initiation of the following segments in the sequence (Mink,
1996).
One may speculate whether this model can explain one of the
main symptoms of stuttering, namely repetitions of the first sound or
syllable of a word. In this case the first component of the phrase is
initiated by structures outside the basal ganglia, but then the basal
ganglia fails, for some reason, to produce a cue that marks the end of the
first component. The result would be that the sequence breaks and the
first component is repeated.
Marsden and Obeso (1994) proposed a model of motor cueing in
Stuttering and the Basal Ganglia 7
which some neurons in the GPi increase their activity in order to
suppress unwanted motor activity in the SMA, while other GPi neurons
reduce their activity to release the wanted motor action. This model
suggests a mechanism for the way in which impaired generation of
timing cues might at the same time lead to the release of dysfunctional
motor activity and the absence of the desired motor activation. This
combination of simultaneous releasing and inhibiting cues can be
generated as a result of the focused vs. diffuse projections of the direct
and the indirect pathways, as discussed in Section 2.
3.6.2. Cueing and signal-to-noise ratio in the direct and indirect
pathways
A prerequisite for a proper function of the suggested shift-cues
from the basal ganglia to the SMA is that there is sufficient contrast
between the releasing cue and the surrounding inhibition, both from a
spatial and a temporal viewpoint. The spatial aspect is related to the
contrast between the focal activation from the direct pathway and the
background inhibition from the indirect pathway. The temporal aspect
refers to the contrast between the amplitude of the cue and the baseline
level of activation in the direct pathway, before and after the cue. These
contrasts can also be viewed as signal-to-noise ratios.
It is likely that there are a large number of ways in which these
signal-to noise ratios may be compromised, for example by floor- or
ceiling-effects, both in the spatial and temporal aspects. It may be
speculated that all types of reduced signal-to noise ratio in these circuits
might lead to disturbed function of the shift-cues, but probably with
some differences in symptomatology. Reduced signal-to-noise ratio due
to a ceiling-effect might be expected to result in a general disinhibition
of motor impulses, while a floor-effect might result in shift-problems
without accessory involuntary movements. The underlying pathology
may be of various types, from lesions to imbalance in basal ganglia
receptor systems.
3.6.3. Cueing and the TANs
It seems likely that these learned movement cues from the basal
ganglia are dependent on the functions of certain interneurons in the
striatum, "Tonically active neurons" (TANs). The TANs are thought to
be cholinergic interneurons, with the ability to modulate both projection
neurons and interneurons in the striatum (Blazquez, Fujii, Kojima, &
Graybiel, 2002). They differ from other neurons in the striatum by
having a high (tonic) firing rate at rest. What make the TANs especially
interesting is that they show signals related to the learning of behavioral
responses, and that these signals are very widely dispersed and
temporally coordinated through the striatum (Graybiel, Aosaki, Flaherty,
& Kimura, 1994). This puts them in a position to serve an integrative
and synchronizing function, important for the timing of movements.
This integrative function is important since the motor circuits
through the putamen are somatotopically organized in parallel, and
mainly segregated (Alexander et al., 1990; Jaeger, Kita, & Wilson,
1994). To coordinate the activity in different muscles these segregated
circuits must be synchronized. It has been suggested that the TANs are
involved in this type of motor binding (Graybiel et al., 1994; Blazquez
et al., 2002). Another type of neurons that may be involved in striatal
synchronization is a small population of GABAergic interneurons which
are connected by electrotonic synapses and have the ability to block a
large number of projection neurons simultaneously (Koos & Tepper,
1999).
3.6.4. Cueing as an effect of practice
The responses in the TANs and in the GP neurons grow stronger
and more well-defined after practice of a certain behavior (Graybiel et
al., 1994; Brotchie et al., 1991). If stuttering is related to impaired
cueing from these neurons, stuttering would be expected to decrease
after practice of a certain speech sequence. Indeed, this seems to be the
case: firstly, the so-called adaptation effect shows that the frequency of
stuttering tends to decrease if the same text is read several times
(Wingate, 1986). Secondly, the more frequently a word occurs in the
language, the smaller is the probability of stuttering (Bloodstein, 1995;
Dayalu, Kalinowski, Stuart, Holbert, & Rastatter, 2002). Increased
practice of a certain sequence may lead to stronger cues from the basal
ganglia and reduction of the stuttering.
Stuttering and the Basal Ganglia 8
4. "Neurogenic" stuttering
4.1. The relation between "neurogenic" and "developmental" stuttering
One way to get information about which structures that may be
involved in stuttering is to analyze the rare cases of stuttering with adult
onset after brain lesions, called neurogenic or acquired stuttering.
Neurogenic stuttering shows both similarities and differences compared
with developmental stuttering (Ringo & Dietrich, 1995). Some cases of
neurogenic stuttering seem to be indistinguishable from developmental
stuttering (Lebrun, Leleux, Rousseau, & Devreux, 1983; Van Borsel &
Taillieu, 2001).
The published reports indicate that the dominant feature of
neurogenic stuttering is repetitions of sounds or syllables, sometimes in
conjunction with prolongations of sounds. Blocks are less frequently
reported. Nevertheless, Heuer, Sataloff, Mandel, and Travers (1996)
reported one case of stuttering after lesion in the left putamen, showing
blocks, frequent use of filler sounds (e.g., "uh"), aversion of eye gaze,
and eye closing during speech blocks. Andy and Bhatnagar (1992)
describe cases of neurogenic stuttering with spasmodic blocks at word
initial position, but without any accessory behaviors such as facial
grimaces or limb movements. In summary, blocks with struggle seem to
be less common in neurogenic stuttering, but there appears to be no
sharp divide between developmental and neurogenic stuttering.
Neurogenic stuttering might be more or less similar to developmental
stuttering depending on the location of the lesion.
Also childhood stuttering can be caused by cerebral lesions. In a
group of 313 persons with known lesions during childhood but with
normal intelligence, Bohme (1968) found that 24% stuttered.
4.2. Localization of lesions in neurogenic stuttering
4.2.1. Problems of localization
Neurogenic stuttering has been reported after lesions to almost all
parts of the brain, except the occipital lobe (Van Borsel, Van Der Made,
& Santens, 2003). The exact location of the lesions in neurogenic
stuttering has often been uncertain, especially in older reports and in
cases with diffuse lesions. At the same time it is almost impossible to
exclude the existence of small undetected lesions. This means that single
cases which are reported to have lesions in structures seemingly
unrelated to theories of neural functions in stuttering have little
explanatory value. Another problem is that lesions in one structure may
disrupt functions of other structures.
4.2.2. Lesions of the basal ganglia-thalamocortical circuit?
Do the published cases of neurogenic stuttering indicate
involvement of the basal ganglia-thalamocortical motor circuit? This
circuit consists of the putamen (striatum), globus pallidus, ventrolateral
(VL) thalamus (Parent, 1996), and cortical motor areas like the SMA.
Indeed, a large proportion of the best documented cases had lesions of
these structures. Ludlow et al. (1987) investigated 10 cases of
neurogenic stuttering caused by missile wounds to the brain in wartime.
The sites of lesions in this group were compared with the sites of lesions
in a group of persons with missile wounds to the brain, but without
speech problems. The only gray matter structures that were significantly
more frequently affected in the stuttering group were the striatum and
the globus pallidus. In 10 persons with stuttering 8 had lesions of these
structures. The left putamen was lesioned in the case reported by Kono,
Hirano, Ueda, and Nakajima (1998), in one of three cases reported by
Heuer et al. (1996), and in two of three cases reported by Ciabarra,
Elkind, Roberts, and Marshall (2000). Cases of neurogenic stuttering
with lesion of the left thalamus have been reported by Van Borsel et al.
(2003) (the VL nucleus), and by Heuer et al. (1996). Further, stuttering
after lesions in the SMA was described by Van Borsel, Van Lierde, Van
Cauwenberge, Guldemont, and Van Orshoven (1998), Ackermann,
Hertrich, Ziegler, and Bitzer (1996), and by Nagafuchi and Takahashi
(1989, as cited in Abe, Yokoyama, and Yorifuji, 1993). Further support
for involvement of the basal ganglia-thalamocortical motor circuit
comes from studies of stimulation of brain regions during surgery with
awake patients. Ojemann and Ward (1971) studied the effect of
stimulation of the left VL thalamus during surgery. The authors report
that stimulation of some points in the VL nucleus resulted in repetition
of the first syllable of words. In a similar way Penfield and Welch
(1951) investigated the responses from stimulation of the SMA. They
found places in the SMA where stimulation elicited repetition of the first
syllable of words.
In summary, it seems clear that lesions of the basal ganglia-
Stuttering and the Basal Ganglia 9
thalamocortical motor circuit are a frequent cause of neurogenic
stuttering. It is, however, very difficult to estimate the portion of the
cases with neurogenic stuttering that is related to basal ganglia
dysfunction.
4.2.3. Lateralization of lesions
Most cases of neurogenic stuttering are reported after lesions to
the left hemisphere, only a few reports of neurogenic stuttering after
right side lesions have been published, for example by Lebrun, Leleux,
and Retif (1987) and by Ludlow, Rosenberg, Salazar, Grafman, and
Smutok (1987). Furthermore, some of these cases might have had
undetected left hemisphere lesions causing the stuttering. In summary,
left hemisphere lesions constitute the bulk of the published cases of
neurogenic stuttering, but it seems that also right side lesions may have
this effect.
4.3. The putamen is influenced by the CM nucleus in the thalamus
As discussed in Section 3.6.3, the TANs in the putamen may play
a key role in the generation of movement related cues from the basal
ganglia. It has been found that the learned responses of the TANs in the
putamen are almost abolished after inactivation of the centremedian
nucleus (CM) in the thalamus (Matsumoto, Minamimoto, Graybiel, &
Kimura, 2001). The CM nucleus is among the largest thalamic nuclei in
humans. Its main projections innervate the entire sensorimotor parts of
the striatum (approximately covering the putamen) (Parent, 1996). An
interesting coincidence is that the CM nucleus has been reported to be
involved in some cases of stuttering.
Andy and Bhatnagar (1992) reported four patients with
neurogenic stuttering who were treated with stimulation of the left CM
nucleus for relief of chronic pain. The treatment resulted in almost total
relief of the stuttering. What could be the mechanism behind this effect?
All cases showed pathologic electrical discharges in the left thalamus
(not seen in the scalp EEG). The authors suggested that the discharges
emanated from low-threshold neurons, which were inactivated by the
low-level stimulation. Their hypothesis was supported by the
observation that mechanical perturbation of the CM nucleus during
surgery of a non-stuttering person elicited electrical discharges and
stuttering, consisting of repetitions of the first syllable (Andy &
Bhatnagar, 1991). One of the cases with acquired stuttering was tested
for chorus reading, which made the speech normal. This suggests that
the stuttering was related to defective internal cues, so that the speech
was normalized by external timing cues from the voice of another
person. Further, these cases showed no adaptation effect, which
indicates that the cueing function was not improved by practice.
Interestingly, none of them developed concomitant symptoms like facial
grimaces, limb movements, or anxiety related to stuttering. All four
cases had repetitions of sounds, syllables, or words, and hesitations.
Two of them exhibited prolongations of sounds. The stuttering occurred
predominantly at word initial position. In summary, these data are in
accord with a model where the neurogenic stuttering was caused by
pathologic signals from the CM nucleus to the putamen, resulting in a
disturbing effect on the TANs and the internal cueing process.
Abe et al. (1993) described a related case, with onset of stuttering
after infarction involving the left CM nucleus. The stuttering consisted
of repetitions of the first syllable in words. A possible interpretation is
that the destruction of the CM nucleus resulted in inactivation of the
TANs in the putamen, as described by Matsumoto et al. (2001), with
disturbance of the cueing function.
4.4. Summary
The lesion research suggests that the basal ganglia circuits
through the putamen may play an important role in many cases of
neurogenic stuttering. Lesions causing stuttering are usually located in
the left hemispheres.
5. Imaging of brain activation in stuttering
In relation to the theme of this paper two main questions may be
asked regarding imaging of cerebral activation: Do brain imaging data
indicate (a) abnormalities in the basal ganglia in persons who stutter,
and (b) activation that might compensate for basal ganglia dysfunctions?
Another aspect is that brain imaging in stuttering has often been related
to the hypothesis that stuttering is caused by anomalous cerebral
lateralization (the cerebral dominance theory (Travis, 1978)), and that
Stuttering and the Basal Ganglia 10
right hemisphere activity may disrupt left hemisphere control of speech.
5.1. Abnormalities in the basal ganglia?
Wu et al. (1995) reported low striatal metabolism in a PET study
of four persons who stuttered. This reduction of metabolism has not,
however, been found in other PET studies. A possible cause of different
results in different studies might be that the stuttering population
consists of subtypes, which could exert a strong influence on the results
of studies with a small number of participants. In another PET study Fox
et al. (1996) found increased activation in the left globus pallidus during
reading with stuttering, compared with fluent reading in controls. The
interpretation of PET-activation in the basal ganglia is, however, quite
difficult. The intrinsic circuits of the basal ganglia are very complex, and
so is the relation between metabolism and signaling in the basal ganglia
structures (Jueptner & Weiller, 1995; Lauritzen, 2001; Waldvogel et al.,
2000).
5.2. Activation compensating for deficient speech automaticity?
If stuttering is related to a dysfunction of automatization of speech
it may be expected that persons who stutter will show increased cerebral
activation due to compensatory strategies, like increased conscious
control of speech initiation. Which pattern of brain activation is related
to non-automatic self-initiated movements? Jenkins, Jahanshahi,
Jueptner, Passingham, and Brooks (2000) used brain imaging (PET) to
investigate activation elicited by self-initiated and irregularly paced
movements with the right index finger, in normal persons. Compared to
rest, the results showed widespread bilateral activation (for example in
the lateral premotor cortex, SMA, and the anterior cingulate cortex) with
slight right hemisphere dominance in most regions, even though it was
the right index finger that was moved. Increased right hemisphere
activation is a very frequent finding in research on stuttering (De Nil,
1999).
Two of the areas with right hemisphere dominance that were
activated by finger movements in Jenkins et al. (2000) were the insula
and the supramarginal gyrus (BA 40). In a PET study of stuttering Braun
et al. (1997) calculated correlations between individual variations of
speech fluency (based on 2-second periods) and brain activation. It was
found that the activation of these structures (the right insula and the right
supramarginal gyrus) correlated with increased fluency (r = 0.7 and
0.52, respectively). De Nil, Kroll, Kapur, and Houle (2000) reported
increased activation of these two regions, with right side dominance,
during oral reading compared with silent reading, in persons who stutter.
This increased activation during reading with stuttering suggests that the
correlations between increased fluency and activation in these regions
(Braun et al.) were not an effect of de-activation during stuttering, but
rather an effect of activation during fluent periods of speech. Activation
of the insula was also found by Fox et al. (1996), but in this study the
activation was bilateral. In summary, the reviewed results support the
suggestion that the right insula and the right supramarginal gyrus were
activated as parts of a non-automatic compensatory system that
decreased stuttering. This interpretation was also suggested by Braun et
al. (1997). Other cortical areas correlating with increased fluency in the
study by Braun et al. were the right frontal operculum (BA 45 and 47)
and the right inferior somatosensory cortex (BA 1, 2, 3, and 43).
In the discussion of the rhythm effect (see Section 3.2) it was
suggested that the lateral premotor cortex and the cerebellum form a
system that compensates for dysfunctions in the basal ganglia-SMA
system. For example, that external cues facilitate movements in
Parkinson's disease through this cerebellar-preMC system (Hanakawa et
al., 1999). Fox et al. (1996) found strong bilateral activation of the
cerebellum in a PET-study of persons who stutter, both during stuttering
and fluent chorus speech. The finding of increased cerebellar activity
during stuttering is supported by Braun et al. (1997) (bilateral
activation), and De Nil et al. (2000) (right side activation). Fox et al.
also found strong activation of the right superior lateral preMC, and De
Nil et al., similarly, reported right hemisphere activation of lateral
preMC regions (BA 6 and 44). It seems quite possible that this
cerebellar and preMC activation reflects attempts to compensate for
dysfunctions in the basal ganglia system.
Another finding that may be an expression of compensatory
activity is the strong increased SMA activation, with right side
dominance, during stuttered speech, reported by Fox et al. (1996) and
Ingham, Fox, Costello, and Zamarripa (2000). If the core problem in
stuttering is that the basal ganglia fail to provide sufficient timing cues
Stuttering and the Basal Ganglia 11
to the SMA, then it might be the case that the SMA gets increased
activation as a consequence of the need for compensatory processing.
5.3. Lateralization and stuttering
A conclusion from the review above is that observations of
increased right hemisphere activation during speech in persons who
stutter are likely to reflect, at least partly, compensatory neural activity.
This explanation does not, however, apply to results indicating
anomalous lateralization of other functions in persons who stutter, such
as perception of language. Examples of this are studies with dichotic
listening (Curry & Gregory, 1969) and tachistoscopic viewing (Moore,
1976; Hand & Haynes, 1983). Nevertheless, it is still possible that these
observations represents an epiphenomenon: If stuttering often is related
to subtle non-specific left hemisphere dysfunctions, the stuttering
population would tend, on average, to show reduced left side dominance
for all functions which normally have left side lateralization, such as
perception of language.
Another problem with the cerebral dominance theory of stuttering
is, as pointed out by Ingham (2001), that females tend to show less left
hemisphere dominance than males, but stuttering is clearly more
common in males. In summary, the arguments for the cerebral
dominance theory of stuttering do not seem convincing.
6. Stuttering and dopamine
6.1. Dopaminergic drugs and stuttering
Beginning in the 1950's dopaminergic drugs were tested for the
treatment of stuttering, mostly using dopamine blockers but also
stimulants. The rationale for trying dopamine blockers was that they
were considered as tranquilizers (Kent, 1963).
6.1.1. Stuttering and D2-receptor blockade
The drug that has been most thoroughly tested for treatment of
stuttering is the D2-blocker haloperidol. Gattuso and Leocata (1962)
claimed very favorable results in children. Since then at least nine
controlled studies have been made with haloperidol and stuttering (see
Brady (1991) for a review), with generally positive results in some of
the subjects. The drug seems to exert its main effect on the severity of
stuttering behavior and not so much on the frequency of stuttering. In a
few cases the improvement was reported to have been dramatic (Healy,
1974), but in most cases the experience of side effects or merely slight
improvement led to termination of treatment. Brady (1991) suggested
that haloperidol is more effective in the treatment of stuttering than most
other neuroleptics due to its high specificity for D2 receptors.
The model of basal ganglia function presented in the introduction
above suggests a possible mechanism of action: D2 receptors are mostly
located on the striatal neurons forming the indirect pathway. Blockade
of these inhibitory receptors will lead to increased activity of the indirect
pathway, thereby strengthening the diffuse inhibition of motor activity.
This explanation is in accordance with the observation that haloperidol
exerts its main effect in reducing superfluous motor activation during
stuttering, not in reducing the number of disruptions. This also means
that D2 blockade might lead to improvement even if the superfluous
motor activity is caused by some other factor than D2 hyperactivity.
6.1.2. Stuttering and stimulants--the possibility of subgroups
Also stimulant drugs, stimulating dopamine and norepinephrine,
have been found to reduce stuttering in some cases. Fish and Bowling
(1962) reported a case of dramatic reduction of stuttering while taking
amphetamine for weight reduction, the improvement persisting also after
medication was discontinued. They conducted a double blind trial with
amphetamine in 22 persons with stuttering and mental retardation. In the
treatment group 5 out of 11 persons improved, while only 1 out of 11 in
the placebo group improved. In 3 of the improved cases the
improvement was claimed to be so great that their whole course in life
was changed, and that the improvement obtained by three months of
treatment was maintained, with only occasional medication for one
patient.
Later Fish and Bowling (1965) investigated if persons with
stuttering and mental retardation, who did not improve on amphetamine,
instead would improve on a D2-receptor blocker. Of 28 persons with
stuttering 14 improved on amphetamine, while 2 deteriorated. The D2-
blocker led to improvement in 8 out of 12 persons who did not improve
on amphetamine. Only 4 out of 26 did not improve on any of the
medications (and they were not improved by a combination of the
Stuttering and the Basal Ganglia 12
drugs).
A similar study was reported by Langova and Moravek (1964),
using a single dose of the stimulant phenmetrazine (proprietary name
Preludin, which has effects similar to amphetamine) and long-term
administration of the D2-blocker chlorpromazine. The participators were
divided into "stuttering" (N = 17 for the stimulant trial and N = 12 for
the D2-blocker trial), "cluttering" (N = 8 and 13), and "stuttering-
cluttering" groups (N = 11). In summary, 88% of the persons with
"stuttering" were regarded as improved by the stimulant, none getting
worse. On the other hand, 67% got worse on the D2-blocker and none
got better. In contrast, the persons with stuttering-cluttering or cluttering
showed the opposite tendencies: 79% got worse on the stimulant and
none got better, while 79% got better on the D2-blocker and only 4%
got worse. The reported subjective feelings also differed between the
groups. The persons with cluttering tended to feel tense and uneasy on
the stimulant and more tranquil on the D2-blocker. The "stuttering"
persons tended to report the reverse, namely unpleasant feelings while
being treated with the D2-blocker and pleasant and more harmonious
feelings with the stimulant.
The results of this study suggest the existence of two
neurochemically different subgroups of stuttering, "stimulant
responsive" and "D2-blocker responsive", relating to the suggested
dichotomy between "stuttering" and "stuttering-cluttering".
Unfortunately, this type of study has not been replicated. However, the
figures in Fish and Bowling (1965) and Langova and Moravek (1964)
are similar if the stuttering and stuttering-cluttering groups are merged:
about half of the persons with stuttering were improved on stimulants
and about one third were improved by D2-blockers.
One problem with the study by Langova and Moravek (1964) is
that the concept of "stuttering-cluttering" seems to be unsubstantiated by
published research, and that the criteria for this diagnosis are not clear.
Daly (1996) described stuttering-cluttering as a disorder with significant
characteristics of both stuttering and cluttering, pertaining not only to
speech but also to symptoms of behavior, motor functions, and
language. Daly lists for example the following traits as frequent among
persons with cluttering: language delay, misarticulation, motor
problems, attention deficits, impatient listening, impulsivity, and
carelessness. Persons with stuttering without cluttering are reported to
have for example the following typical traits: tense pauses in speech,
being fearful and anxious about speech, using starter sounds and word
substitutions, showing more stuttering under pressure, and having fluent
episodes. Daly's description seems to roughly fit Van Riper's (1982)
characterization of developmental tracks in stuttering: tracks I and III
corresponding to "stuttering" and track II corresponding to "stuttering-
cluttering". According to Daly about 40% of the persons who stutter
may be classified into the stuttering-cluttering group. In contrast, a study
of 2628 stuttering school children, based on reports from speech-
language pathologists, found cluttering in only 0,7% of the children
(Blood, Ridenour, Qualls, & Hammer, 2003). It seems clear that
different criteria for the diagnosis of cluttering have been used. There is
an obvious need for further research to clarify these aspects, and to
investigate the possibility of two pharmacologically distinct subgroups.
In interviews with three adults who stutter the author of this paper
has obtained personal reports of the effects of various drugs on
stuttering, supporting the importance of complex neurochemical factors
as well as supporting the heterogeneity in responses. In all these cases
the drugs were used for recreational purposes, for short periods of time.
The first case claimed that his stuttering made him almost mute when
using marijuana, which at the same time improved his creativity. On the
other hand, alcohol was said to make his speech almost normal, with
deterioration afterwards. He noticed no difference in his speech when
trying amphetamine. The second case reported clearly reduced stuttering
during use of amphetamine. The third case, with severe stuttering, told
how when trying ecstasy (MDMA) twice he spoke fluently for some
hours, also according to his friends. Amphetamine did not affect his
speech.
The claim of the effect of ecstasy on stuttering is especially
interesting in the context of basal ganglia functions, since a case of
remarkable improvement of motor symptoms in Parkinson's disease has
been reported in the media (BBC Horizon, 2001). This anti-parkinsonian
effect of ecstasy has been confirmed in studies of primates (Iravani,
Jackson, Kuoppamaki, Smith, & Jenner, 2003). Investigations of this
effect of ecstasy points to a serotonergic mechanism, indirectly
modulating the dopamine system. The exact mechanism is still not
Stuttering and the Basal Ganglia 13
known, but an agonist effect on serotonin receptor subtype 5-HT1a or 1b
is suggested (Iravani et al.). It is interesting to note that the anti-
parkinsonian effect in primates was fully blocked by the selective
serotonin reuptake inhibitor (SSRI) fluvoxamine (Iravani et al.).
Ecstasy is not suitable for the treatment of stuttering, because of a
suspected risk that it might induce Parkinson's disease (Kuniyoshi &
Jankovic, 2003) and because of the risk of misuse and addiction.
However, the possibility of influencing dopamine functions and basal
ganglia motor symptoms through serotonergic mechanisms is
interesting. Effects of other serotonergic drugs have been reported in
stuttering, especially for the SSRI paroxetine (see for example Schreiber
and Pick (1997), Costa and Kroll (2000), Boldrini, Rossi, and Placidi
(2003)). The author of this paper has interviewed a stuttering man who
experienced long-lasting and clear improvement of speech on
paroxetine, after about 3 weeks. When he stopped and restarted
medication the stuttering changed accordingly. He claimed that another
SSRI, citalopram, did not improve speech. There are indications of
subtle differences in pharmacological effects between different SSRIs,
and that paroxetine shows similarities with agonists for the 5-HT1a
receptor (Sokolowski & Seiden, 1999). As discussed above, an agonist
effect on the 5-HT1a receptor has also been suggested for ecstasy
(Iravani et al., 2003). It is possible that paroxetine and ecstasy affect
stuttering through the same pathway.
In this context it should be mentioned that severe psychiatric
withdrawal symptoms, with hypomania, irritability, and intrusive
thoughts, has been reported for two stuttering men after discontinuing
high-dose (50 mg) paroxetine treatment (Bloch, Stager, Braun, &
Rubinow, 1995). This risk should be considered if trying paroxetine. If
withdrawal symptoms occur the dose should be tapered slowly. The
studies reporting an effect of paroxetine on stuttering used a lower dose,
usually 20 mg.
6.1.3. Drug-induced stuttering
Some cases of drug-induced stuttering can be found in the
literature. Burd and Kerbeshian (1991) reported a case of a 3-year-old
girl who was treated for hyperactivity. Stimulants resulted in stuttering
that disappeared on discontinuation of the drugs. Interestingly, the
medications had no effect on the hyperactivity. Also D2-blockers have
been reported to induce stuttering (Brady, 1998). This is in line with the
results reported above, that both stimulants and D2-blockers can make
stuttering worse, but in different subgroups.
6.2. Stuttering and FDOPA-PET
One of the most remarkable reports in the research on stuttering
comes from a brain imaging study using FDOPA-PET, by Wu et al.
(1997). FDOPA is a precursor of dopamine, intended to measure the rate
of dopamine synthesis in the brain (Barrio, Huang, & Phelps, 1997). The
persons who stuttered showed about 3 times higher uptake of FDOPA in
many parts of the brain, compared with the controls. The study is limited
by the small number of participants, three persons who stuttered, but
even so the result was statistically significant.
How can this result be interpreted? If the measurements are
correct they imply that at least a substantial subgroup of persons who
stutter have a deviant dopamine system. The results of the treatment trial
by Langova and Moravek (1964), discussed above, suggests the
existence of biochemically different subgroups. It may well be the case
that the result of this study of FDOPA represents only one of these
subgroups.
6.3. Temperament and motor activity
6.3.1. Temperamental and gross motor effects of dopamine
If stuttering is related to deviations in dopamine functions, are
there any indications of this in gross motor activity or in temperament?
Motor effects of dopamine have been demonstrated in mice lacking the
gene for the dopamine reuptake transporter. These mice have a raised
level of dopamine in the synaptic cleft and are very hyperactive (Giros,
Jaber, Jones, Wightman, & Caron, 1996). Cocaine acts in the same way,
blocking the reuptake of dopamine. At moderate doses some of the
effects of cocaine are motor excitement, talkativeness, mood
amplification (both euphoria and dysphoria), and heightened energy.
Higher doses may result in motor stereotypies, irritability or anxiety
(Feldman, Meyer, & Quenzer, 1997). In research on personality
differences high dopamine activation is mainly related to traits like
behavioral activation and impulsive sensation seeking (Depue & Collins,
1999; Pickering & Gray, 1999), but a relation to increased anxiety and
Stuttering and the Basal Ganglia 14
neuroticism has also been suggested (Derryberry & Reed, 1999).
In summary, dopamine seems to have an activating effect, both
motor and temperamental, but might also, at higher levels, increase
anxiety. This is in accord with the model of basal ganglia function
presented in the introduction: dopamine facilitates motor, cognitive and
limbic impulses. It is possible that high dopamine activation can lead to
increased responsiveness to both rewarding and threatening stimuli.
6.3.2. Temperamental and gross motor tendencies in stuttering
Comings et al. (1996) investigated the effects of different variants
of dopamine-related genes in persons with Tourette syndrome, their
relatives, and in controls. A variant of the D2-receptor gene was
significantly related to increased frequency of stuttering, mania, ADHD,
tics, and obsessive-compulsive disorder. The relationships were weak,
although statistically significant.
Embrechts, Ebben, Franke, and van de Poel (2000) studied the
temperament of 38 stuttering and 38 non-stuttering children aged three
to seven years. Temperament was evaluated by a questionnaire to the
caregivers. The result showed that the stuttering group had a
significantly higher level of gross motor activity and of impulsivity, and
significantly lower attentional focusing, inhibitory control (capacity to
suppress inappropriate approach responses), and perceptual sensitivity
(detection of low intensity stimuli). It is also interesting to note that the
stuttering group had lower scores in shyness, fear and sadness, though
not significantly lower. The largest group difference was in gross motor
activity level.
Oyler (1994) investigated the personality of 25 stuttering and 25
nonstuttering children aged 7 to 12 years. She reported higher
"sensitivity" in the stuttering group. Other significant differences were
higher frequency of problems of learning, language, attention and motor
coordination, and higher frequency of family history of problems with
language, attention, and hyperactivity.
In summary, the results above repeatedly suggest increased
behavioral activation in persons with stuttering, both motor and
temperamental. This is in line with the effects of high dopamine
activation but other causes are quite possible. The results also show the
main symptoms of attentional deficit hyperactivity disorder (ADHD)
(Schachar & Tannock, 2002). As discussed above, traits like motor
hyperactivity, attention deficits, and impulsivity seem to be typical of
persons with "stuttering-cluttering" but not of persons with "pure
stuttering": the traits of ADHD might be limited to this stuttering-
cluttering subgroup. This points to the importance of considering
subgroups and not only looking at the overall mean.
6.4. Stuttering and ADHD
Is stuttering frequent in persons with ADHD? Biederman et al.
(1993) reported 13% lifetime incidence of stuttering in a group of 120
adults with ADHD, compared with 2% in controls. A group of 140
children with ADHD (mean age 10.5 years) had only a 3.6% incidence
of stuttering. The result of this study suggests that stuttering and ADHD
do not have a strong relation in childhood, and that ADHD combined
with stuttering tends to be more persistent than ADHD in general,
resulting in a higher lifetime incidence of stuttering in adults with
ADHD.
There are some indications that ADHD with stuttering may be
neurochemically different from most cases of ADHD. About 74% of
adults with ADHD tend to improve on stimulants (Faraone et al., 2000),
while Langova and Moravek (1964) found that 79% of persons with
stuttering-cluttering or cluttering (who often seem to have traits of
ADHD) got worse on a stimulant, and none got better. Burd and
Kerbeshian (1991) described a hyperactive child who got transient
stuttering as a side-effect of stimulants, but no improvement in the
hyperactivity. However, this pattern may not be consistent, since
anecdotal information suggests that some cases with ADHD and
stuttering are treated successfully with stimulants.
Another question is if the increased behavioral activation shown
by some cases of stuttering should be regarded as a type of ADHD or a
type of "hypomania". Brody (2001) suggests that ADHD and mania (or
hypomania) are confounded in most existing research. Brody considers
impairment of executive functions to be a characteristic of ADHD, but
not of mania.
6.5. Is stuttering a motor stereotypy?
Stereotypy (repetitive behavior patterns) is a feature of many
neurologic and psychiatric disorders. It can range from repetition of
Stuttering and the Basal Ganglia 15
single movements to complex behaviors or cognitive stereotypies like in
obsessive-compulsive disorder. The basal ganglia are suggested to be
central for the expression of stereotypies, and motor stereotypies can be
induced by dopamine stimulating drugs (Canales & Graybiel, 2000).
An important objection may be raised against a suggestion of
stuttering as a stereotypy: Stereotypic repetitions seem to be, at least
partly, based on some type of drive to execute the behavior (Graybiel,
Canales, & Capper-Loup, 2000). In stuttering there is hardly any ground
for suspecting that the repetitions are based on a drive to repeat that
specific segment. Instead it is more reasonable to suppose that the
repetitions are merely the result of an inability to continue to the next
segment in the sequence. An observation supporting this contention is
that persons with stuttering normally do not repeat the final segment of a
phrase (Rosenbek, Messert, Collins, & Wertz, 1978; Bloodstein, 1995).
Nevertheless, there may be a subgroup of persons with
"stuttering" who really do show a stereotypic speech disorder. These are
the rare cases which Van Riper (1982) refers to as stuttering track IV.
Van Riper described their stuttering as highly stereotyped, almost
deliberate. A characteristic feature is lengthy repetitions of words
already spoken normally. Few signs of avoidance or fear are shown. The
speech repetitions are often accompanied by other symptoms like
stereotyped postures, grunting, biting, or tongue protrusion. The
diagnosis Tourette syndrome with palilalia (Bruun, Cohen, & Leckman,
1984; Graybiel & Canales, 2001) seems to fit well with the
characteristics of this group. Tourette syndrome is a neuropsychiatric
syndrome characterized by complex tics. The pathophysiology most
likely involves the caudate nucleus in the basal ganglia (Wolf et al.,
1996).
6.6. Stuttering, emotions, and learning
6.6.1. Emotions and basal ganglia disorders
It is a common clinical experience that stuttering is influenced by
emotional reactions and stress. This aspect is well compatible with the
model of stuttering as a basal ganglia disorder. Victor and Ropper
(2001) write in a textbook of neurology that "Stress and nervous tension
characteristically worsen both the motor deficiency and the abnormal
movements in all extrapyramidal [basal ganglia] syndromes, just as
relaxation improves them" (p. 75).
6.6.2. Emotional variations in dopamine release?
The dopamine neurons in the substantia nigra pars compacta
(SNc) project to the striatum, providing a dense dopaminergic input.
Normally these neurons have a tonic firing rate, providing a low, well
regulated, extracellular level of dopamine (Schultz, 1998). An
interesting aspect is that the dopamine neurons have been found to show
rapid variations of their firing rate according to the situation. Increased
release of dopamine in the striatum has been shown to strengthen active
synapses between cortical and striatal neurons, and to facilitate learning
of behaviors (Reynolds et al., 2001). However, the pattern and
functional consequences of these "phasic" variations of dopamine are
still a matter of debate.
The reward prediction error model (Schultz, 1998) states that the
dopamine neurons vary their firing rate in relation to prediction of
rewards. Events that are more rewarding than predicted will increase the
release of dopamine, while omission of a predicted reward will lead to
reduction of dopamine release (Schultz & Dickinson, 2000). These
error-related responses of the dopamine neurons would make them
suited to constitute a teaching signal for learning of behavioral responses
(Waelti, Dickinson, & Schultz, 2001), with strengthening of behaviors
that were more rewarding than predicted and weakening of behaviors
that failed to produce the predicted reward. This model of dopamine
variation might be relevant for automatization of speech motor patterns,
since (a) reward-related variation in the dopamine release has been
found in the putamen (Schultz, 2000), which is the sensorimotor region
of the striatum, and (b) simulation of a neural network indicates that the
reward-related changes of dopamine release constitute an excellent
teaching signal for learning of sequential movements (Suri & Schultz,
1998).
Such a mechanism would be of interest in relation to the
development and treatment of stuttering. A negative emotional
experience of stuttering could be described as an event that was less
rewarding than predicted, thereby reducing dopamine release and
weakening the motor program for the intended speech sequence that
failed. This mechanism might result in a "vicious circle", where negative
experiences of stuttering lead to increased stuttering, etc. On the other
Stuttering and the Basal Ganglia 16
hand, positive emotional experiences of a functional speech pattern
would tend to strengthen the automaticity of this pattern.
The validity of this reward-prediction model has, however, been
questioned, partly because it has been shown that also aversive and
neutral stimuli may trigger phasic dopamine release. An alternative
model of dopamine functioning was described by Horvitz (2002). This
model states that phasic increase of dopamine reflects salient unexpected
events, regardless of wheather they are rewarding, neutral, or aversive.
Horvitz did not, however, rule out the possibility that future research
may show that the reward-model suggested by Schultz is correct, since
there are some indications that the nature of dopamine responses to
rewards differs from dopamine responses to non-reward stimuli. Such a
difference might result in different effects on the synapses in the
striatum.
6.6.3. Emotional states, dopamine, and stuttering
It has been reported that some persons who stutter temporarily
became "almost magically fluent speakers" when they fell in love, and
that "loving" a vocation or a situation facilitates speech fluency
(Starkweather, 1996). On the other hand, Mowrer (1998) reported the
appearance and disappearance of stuttering in a 2.5-year-old boy in
accordance with the appearance and disappearance of fearful events.
Onset of stuttering in relation to emotional stress has been reported both
in children (Sermas & Cox, 1982) and adults (Roth, Aronson, & Davis,
1989).
It might be speculated that this emotional influence is partly
related to emotionally induced variations in the release of dopamine. It
may be noteworthy that the learned responses in the tonically active
neurons (TANs) in the striatum have been found to be abolished after
dopamine depletion, but are restored by a dopamine receptor agonist
(apomorphine) (Aosaki, Graybiel, & Kimura, 1994). If some cases of
stuttering are related to a sub-optimal level of synaptic dopamine,
emotional events that affect the release of dopamine may have a direct
effect on the severity of stuttering.
This suggestion is supported by a recent brain imaging study
using a dopamine receptor ligand (Goerendt et al., 2003). The study
indicated that release of dopamine in the striatum is involved in the
execution of pre-learned movement sequences. The authors suggest that
it is increased tonic release of dopamine, and not phasic release, that is
important for facilitation of initiation and sequencing of movements. It
seems possible that emotionally related suppression of dopamine release
might impair the execution of automated sequential movements, like
speech.
7. Stuttering and dystonia
7.1. Introduction
Similarities between stuttering and dystonia have been suggested
by Kiziltan and Akalin (1996). The term dystonia signifies motor
symptoms characterized by involuntary muscular contractions, often in
the form of co-contractions where the agonist and the antagonist
muscles are activated simultaneously, with spreading of contraction to
adjacent muscles. Dystonia can affect a specific part of the body, like a
hand or an eyelid (focal dystonia), or it can affect most parts of the
body. (Friedman & Standaert, 2001) In a similar way, many cases of
stuttering also show excessive muscular tension in various parts of the
body. For example, there are reports of co-contraction and inappropriate
tension in laryngeal adductor and abductor muscles in some cases of
stuttering (Freeman, 1979; Freeman & Ushijima, 1978; Shapiro, 1980).
7.2. Dystonia and the basal ganglia
7.2.1. Dystonia and basal ganglia lesions
There are strong indications for a relationship between dystonia
and basal ganglia dysfunction (Friedman & Standaert, 2001). Bhatia and
Marsden (1994) studied the consequences of small isolated lesions of
the putamen. In 15 out of 20 cases the main symptom was dystonia.
Using magnetic resonance imaging (MRI) Rondot, Bathien, Tempier,
and Fredy (2001) investigated the localization in 40 cases of dystonia
with observable cerebral lesions. In 21 cases the location was the
striatum, in 6 the globus pallidus, in 7 the thalamus, and in 6 the
midbrain. All these locations are related to the basal ganglia circuits. In
a study with transcranial ultrasound Naumann, Becker, Toyka, Supprian,
and Reiners (1996) found that 44 out of 57 persons with idiopathic
dystonia (cervical or generalized dystonia, or writer's cramp), showed
Stuttering and the Basal Ganglia 17
increased signal in focal points in the putamen or in globus pallidus,
contralateral to the affected muscles.
7.2.2. Dystonia and reduced inhibition of the cortex
Increased cortical, spinal and brain stem excitability has been
reported in dystonia, and has been suggested to be consequences of
basal ganglia disturbances (Chen, Wassermann, Canos, & Hallett, 1997).
These results are in line with findings of reduced output from the globus
pallidus pars interna (GPi) in dystonia (Vitek et al., 1999) which would
result in reduced inhibition of the target structures. Reduced output from
the GPi could, in turn, be the result of lesions of the putamen, according
to the model presented in Figure 1. Focal lesions of the putamen would
result in loss of neurons in both the direct and indirect pathways, with
loss of the background inhibition provided by the indirect pathway
(reflected in reduced GPi output) and loss of the focal cues provided by
the direct pathway. This may lead to a combination of difficulties to
initiate segments in a movement sequence (due to loss of the direct
pathway) and impaired inhibition of involuntary muscular contractions.
7.3 Dystonia and dopamine
Some cases of dystonia are related to the dopamine system, and,
in parallel to the findings about stuttering discussed in Section 6.1.2,
also dystonia seems to be a neurochemically heterogeneous disorder.
Some cases are improved by L-dopa, increasing dopamine synthesis,
and dystonia can also be an early symptom of Parkinson's disease
(Perlmutter, Tempel, Black, Parkinson, & Todd, 1997). Other cases
show amelioration by a dopamine-depleting and dopamine-receptor-
blocking drug, tetrabenazine (Jankovic & Beach, 1997). Furthermore,
both D2-blockers and L-dopa can cause acute dystonia as a side-effect
(Victor & Ropper, 2001).
Another link between dystonia, dopamine and stuttering comes
from genetic research on torsion dystonia. Early-onset torsion dystonia
is a disorder characterized by dystonic movements and postures, which
in most cases are caused by a single gene. About 30 to 40% of the
carriers of the gene develop the disorder (Augood et al., 1998). Fletcher,
Harding, and Marsden (1991) reported that 8 out of 71 persons with
torsion dystonia had a family history of stuttering, compared with only 1
person in the control group. The gene that causes torsion dystonia is
mostly expressed in the substantia nigra pars compacta (Augood et al.,
1998), which provides the dopaminergic innervation to the putamen.
This implies a disturbance of dopamine function in the etiology of
torsion dystonia. The high incidence of a family history of stuttering
suggests that this dopaminergic dysfunction also increases the risk of
stuttering.
7.4. Task-specificity
An interesting aspect of focal dystonia is that it often is task-
specific, being present for example when a person is walking forward
but not when walking backward or when dancing. Some types of
dystonia have been called "occupational cramps", affecting highly
automated sequential motor tasks like writing with a pen (writer's
cramp), typing, playing a certain musical instrument, or using a
telegraph. Victor and Ropper (2001) describe these disorders: " In each
case a delicate motor skill, perfected by years of practice and performed
almost automatically, suddenly comes to require a conscious and
labored effort for its execution. Discreate movements are impaired by a
spreading innervation of unneeded muscles ..." (p. 116) This task-
specificity, together with the observation that dystonia often gets worse
under stress, has sometimes led to the incorrect conclusion that task-
specific dystonia is psychogenic (Sheehy & Marsden, 1982). Also,
stuttering tends to be highly task-specific: The apparent motor problems
are limited to speech, and the symptoms are often reduced if changing to
a non-automatic way of speaking, like using a foreign accent
(Bloodstein, 1995).
7.5. Fast sequential movements—expansion of cortical maps and
increased gain
7.5.1. Expansion of cortical maps
Task-specific dystonia especially affects certain types of behavior,
like writing, typing, or playing the piano. The highest incidence, 14%,
has been reported in telegraphists (Sheehy & Marsden, 1982). The
affected behaviors tend to be sequential, fast, and well-learned. A reason
why this type of behaviors tends to be affected by dystonia may be
cortical plasticity. Byl, Merzenich, and Jenkins (1996) studied the effect
Stuttering and the Basal Ganglia 18
of repeated stereotyped rapid hand movements (opening and closing of
the hand) in two monkeys. During the test period (several months) both
monkeys developed a movement control disorder. Electrophysiologic
mapping of the primary sensory cortex showed dedifferentiation of
cortical representations of the skin of the hands--the receptive fields
were 10 to 20 times larger than normal. Many receptive fields extended
across two or more digits.
This effect could be explained by integrative plasticity in the
primary sensory cortex, so that somatosensory inputs which are
repeatedly activated simultaneously (within a time period of about 10 to
100 ms) will become integrated into one receptive field (Byl et al.,
1996). If the hand is opened and closed very fast, the muscular afferents
from the flexor and the extensor muscles may become summarized in
the sensory cortex. The normal somatosensory map is degraded and the
ability to control individual muscles becomes impaired. This model
might explain why telegraphists have the highest incidence of dystonia:
they make about 9 muscular contractions per second, more than twice as
many as a typist (Sheehy & Marsden, 1982). Faster repetitions and
highly stereotyped movements increase the risk of sensory integration of
different muscles. Another prerequisite for development of sensory
degradation is that the behavior is consciously attended to. Behaviors
performed automatically do not give significant sensory plasticity (Byl
et al., 1996).
Also the motor cortex can develop expanded representations as a
result of motor practice. It has been found that the degree of motor
cortex plasticity is strongly dependent on the level of GABA-based
inhibition of the cortex (Ziemann, Muellbacher, Hallett, & Cohen, 2001;
Butefisch et al., 2000). Ziemann et al. (2001) demonstrated that a
decrease of GABAergic inhibition of the cortex in combination with
motor practice resulted in a dramatic increase of indications of expanded
representation in the motor cortex. The increase was paralleled by an
increase in peak movement acceleration.
7.5.2 Increased gain in sensorimotor loops
Sanger and Merzenich (2000) have proposed a computational
model of task-specific focal dystonia. Their suggestion is that writer's
cramp and similar disorders are the manifestation of a sensorimotor loop
with a gain > 1. The gain of a loop is > 1 if the output of the loop is
stronger than the input. If so, the signal will be amplified so that it gets
out of control (similar to the effect of putting a microphone too close to
a connected loudspeaker). The authors suggest that this increase in gain
may result from expansion of the cortex area representing a limb, either
in the sensory or motor cortex. This model is in accord with several
aspects of dystonia: (a) increased motor cortex excitability; (b) the
prevalence of basal ganglia disturbances which are likely to result in
disinhibition of the cortex; (c) behaviors likely to result in cortical
plasticity are especially affected by dystonia; and (d) blockade of
feedback often relieves the problem.
7.6. Sensory effects in dystonia and stuttering
Another parallel between stuttering and dystonia is that both
disorders often are much improved by blocking or altering the sensory
feedback ("sensory" here also includes auditory feedback). Blockade of
muscle afferents by lidocaine injection has been shown to abolish co-
contractions in writer's cramp (Kaji et al., 1995). A similar effect is
demonstrated by the "sensory trick" in dystonia: tactile sensory
stimulation of the affected body part often dramatically reduces the
muscular contractions (Kaji, 2001). In stuttering there are reports of
cases where anesthetization of the larynx has led to marked reduction of
the speech problems (Dworkin, Culatta, Abkarian, & Meleca, 2002;
Webster & Gould, 1975, as cited in Bloodstein, 1995). Furthermore,
masking of auditory feedback (MAF) has been shown to alleviate
stuttering (Burke, 1969; MacCulloch, Eaton, & Long, 1970), as well as
frequency shift of the auditory feedback (FAF) (Hargrave, Kalinowski,
Stuart, Armson, & Jones, 1994), or delaying the auditory feedback
(DAF) (Van Riper, 1982).
An interesting observation was made by Dewar, Dewar, and
Anthony (1976): "ex-stammerers" exhibiting fluent speech still showed
abnormal contractions of face muscles, which were abolished by
masking of the auditory feedback. This finding indicates that stuttering
might be related to "dystonic" activity in facial muscles also during
fluent speech, and that this activity may be normalized by blockade of
the auditory feedback.
If stuttering is reduced by masking noise, is there a relation
between stuttering and impairment of hearing? Van Riper (1982)
Stuttering and the Basal Ganglia 19
reported that he had authenticated a case where an adult male, with
severe stuttering since childhood, "immediately stopped stuttering
completely after an accident in which he became completely deafened"
(p. 383-384). Further, an old investigation among 14 458 deaf children
in oral speaking schools reported only 8 cases (0.05%) of stuttering
(Harms & Malone, 1939). However, the ability of masking noise to
improve stuttering does not seem to be dependent on a total masking of
the auditory feedback, since reduction of stuttering also has been shown
when only one ear is exposed to noise (Yairi, 1976).
A curious observation was reported by Baron, Legent, Nedelec,
and Venisse (1969). A 17-year-old male had stuttered since early
childhood, and had also had chronic otitis in the left ear, starting at age 2
or 3. The hearing of the left ear was clearly impaired and the patient also
complained of a certain discomfort when exposed to noise or music.
Diplacusis was suspected. It was noticed that if the patient blocked the
right ear with a cotton wad both the stuttering and the discomfort for
sounds disappeared. The effect was consistent, and at the time of report
the patient had spoken normally for two months with a cotton wad. This
case exemplifies the complex role of hearing in some cases of stuttering.
What might be the mechanisms behind the sensory effects in
dystonia and stuttering? With the background of the reasoning about
dysfunctional automatization and excessive gain in sensorimotor loops,
two related and additive mechanisms are suggested: (a) De-
automatization. Somatosensory and auditory feedback serve as input to
the putamen (Yeterian & Pandya, 1998). The basal ganglia act to
execute automated behaviors based on the habituated environmental
context (Wise, Murray, & Gerfen, 1996). Therefore it is likely that
altering the feedback will result in de-automatization. (b) Reduction of
feedback gain. As discussed above in Section 7.5.2, reducing the
strength of the feedback would reduce the risk for signal overflow in
sensorimotor loops.
Loss of hearing and MAF clearly implies reduced feedback gain,
maybe resulting in de-automatization. FAF is likely to result in de-
automatization because of the dramatic change in the character of the
feedback sound. The effects of DAF might be more complex. DAF with
a long delay, for example 150 ms, tends to result in reduced speech rate,
implying marked de-automatization. A shorter delay, like 50 ms, usually
has little effect on the speech rate but still improves fluency in many
cases. A brief delay means that the feedback circuit becomes slower, and
that the beginning of each speech segment will be produced with
reduced auditory feedback. The effects of this change in the auditory
circuit may be complex, but it seems likely that some degree of de-
automatization will occur.
In summary, the symptoms of task-specific dystonia and
stuttering seem to be related to automatic processing that has become
dysfunctional. It is suggested that the sensory effects (for example the
effect of frequency altered feedback in stuttering) are related to de-
automatization of context dependent processing, and attenuation of the
sensory feedback.
7.7. Arguments against similarity between stuttering and dystonia
7.7.1. Stuttering as a tic disorder
The concept of stuttering as a type of dystonia has recently been
challenged by a study of the character of the involuntary movements
related to stuttering (Mulligan, Anderson, Jones, Williams, &
Donaldson, 2003). These movements were compared with different
types of movements seen in various basal ganglia movement disorders.
The result of this study was that most of the involuntary movements in
stuttering persons during speech could be classified as complex or
simple motor tics. Only a few instances (of squeezing eye closure) were
judged as dystonic. The authors suggested that stuttering is a tic disorder
due to basal ganglia dysfunction.
Two main objections may be raised against the proposal of
stuttering being a tic disorder. The first is related to the subjective
experience. In a review of tic disorders, including Tourette syndrome,
Leckman and Cohen (2003) write: "By the age of 10 years, most
individuals with tics are aware of premonitory urges that may be
experienced either as a focal perception in a particular body region
where the tic is about to occur (like an itch or a tickling sensation) or as
a generalized awareness felt throughout the body. … Most patients also
report a fleeting sense of relief after a bout of tics has occurred." (p. 593)
This type of "urge" and relief does not seem typical for stuttering.
The second objection is that the typical involuntary movements
seen in stuttering are strictly task-related, emerging when trying to
Stuttering and the Basal Ganglia 20
speak. The movements are not shown during other activities. Such strict
task-specificity is often shown in dystonia but does not seem to be
displayed in tic disorders.
It should also be noted that this study is based on a relatively
small group, 16 stuttering adults, of which only one case was classified
as very severe while the rest were regarded as being of moderate to very
mild severity. The total samples of reading and free speech included 600
words for each person. The representativity of this material seems
uncertain and further studies would be important. It may be the case that
stuttering shares characteristics with several different basal ganglia
disorders, like dystonia, parkinsonism, and tic disorders, but that it can
not be defined as any of these.
7.7.2. Stuttering and cortical excitability
Another challenge against the similarities between stuttering and
dystonia comes from a recent report of intracortical inhibition in
developmental stuttering, by Sommer, Wischer, Tergau, and Paulus
(2003). The basis for this investigation was that reduced intracortical
inhibition has been found in focal dystonias like writer's cramp and
blepharospasm (spasm of the eyelid), by measuring the motor response
in a finger elicited by paired-pulse transcranial magnetic stimulation
(TMS). The result of this study indicated that the group of 18 adults with
developmental stuttering had normal intracortical inhibition and
facilitation. Further, the tests with TMS pointed to a raised motor
threshold in the stuttering group. (It may be speculated if this result is
related to findings of increased cortical gyrification in the region
superior of the lateral sulcus (Foundas, Bollich, Corey, Hurley, &
Heilman, 2001), and to disturbances in the structure of the white matter
related to the sensorimotor cortex (Sommer, Koch, PaulusW., Weiller,
& Buchel, 2002). These findings are discussed in more detail below, see
Section 10.)
The reported normal intracortical inhibition and the raised motor
threshold for the finger motor region in persons who stutter suggest a
difference in pathologic mechanisms between focal dystonias and
stuttering. It is too early, however, to dismiss the possible parallel
between stuttering and dystonia based on this one study. For example, a
dystonic disturbance in stuttering might be related to systems not
involved in finger movements, like the auditory system. Further
investigations of these aspects are of importance.
7.8. Summary, dystonia and stuttering
There are several similarities between dystonia and stuttering. (a)
Lesions: The most common locations of lesions causing dystonia are the
putamen or the globus pallidus, and this may also be the case for
stuttering (Ludlow et al., 1987). (b) Pharmacology: Some cases of
dystonia are responsive to dopaminergic drugs, either by inhibiting or
stimulating the dopamine system. Analogous results have been reported
for stuttering (see Section 6.1). (c) Task-specificity: Dystonia is often
limited to highly specific tasks, especially those involving highly
automated sequential movements. The same is the case for stuttering. (d)
Sensory effects: Both dystonia and stuttering are often improved by
blocking or altering the sensory feedback.
Also some differences between stuttering and dystonia have been
proposed: (a) That involuntary movements related to stuttering may be
more similar to tics than to dystonia, and (b) that cases of focal dystonia
tend to show reduced intracortical inhibition while this has not been
found in stuttering.
8. Negative and positive symptoms of stuttering
Stuttering is related to a range of motor symptoms (like various
types of repetitions, blocks, and accessory motor behaviors) and maybe
also to temperamental traits like increased behavioral activation. Some
persons who stutter show only one or a few of these symptoms, while
others have many.
A classic way to structure complex symptoms, especially in basal
ganglia disorders, is to differentiate between negative and positive
symptoms. By negative symptoms is meant the absence of normal
functions, and by positive symptoms the presence of abnormal
activation of behaviors, emotions, or cognitions. This dichotomy is often
used when classifying basal ganglia motor disorders, with hypo- or
akinesia as negative, and chorea, dystonia, tics, tremor, and rigidity as
positive. Positive symptoms can be regarded as signs of disinhibition of
functional parts of the nervous system (Victor & Ropper, 2001). An
analogous division is used regarding symptoms of schizophrenia, with
Stuttering and the Basal Ganglia 21
absence of normal social and interpersonal behaviors as negative, and
psychotic features as positive (Kandel, 2000).
Some symptoms of stuttering and accompanying traits may be
easily classified according to this scheme. Speech blocks involving
increased muscular tension and accessory motor behaviors clearly
include "positive" symptoms. Likewise, anxiety and traits of increased
behavioral activation could also be regarded as positive since they
represent increased activation of a normal function (speech-related
anxiety may, however, well be regarded as a normal reaction). The
classification of speech symptoms like repetitions and prolongations is
more complex. It is possible that similar speech disruptions can occur
both as negative or positive symptoms: The inability to continue the
speech sequence might appear because of a lack of cues or programming
for the following segment, or because of muscular hyperactivation that
disrupts the phonation or articulation. Or, possibly, a combination of
both factors, for example that deficient cues releases inappropriate
muscular activation. It seems likely that these patterns differ between
different persons who stutter, and maybe also between different stages in
the development of stuttering. A more detailed mapping of the proximal
causes of the speech disruptions in stuttering individuals and subgroups
would be a valuable step for the understanding of stuttering. This type of
analysis might reveal constellations of positive vs. negative symptoms,
indicating differences in pathology.
9. Cerebral development, aging, and degeneration
When discussing possible mechanisms of stuttering it is important
to consider age- and gender-related aspects of the disorder. Stuttering
has a typical pattern of onset in early childhood followed by a high rate
of childhood recovery. When looking at developmental aspects it may
also be interesting to study changes of stuttering in older age, and effects
of neural degeneration and lesions. In this section data regarding gender
differences, development, aging, and degeneration will be briefly
reviewed, and possible neural mechanisms will be discussed.
9.1. Age of onset, recovery, and gender ratio
The data regarding age of onset, frequency of recovery, and sex
ratio differ somewhat between different studies, but the general
tendencies are quite consistent. Based on data from some of the more
recent studies (Yairi & Ambrose, 1992, 1999; Månsson, 2000) the
following brief summary may be made: These studies suggest a mean
age of onset between 2.5 and 3 years, a male/female ratio in children of
about 2:1, a recovery rate of about 60-70% within 2 years after onset of
stuttering and further recoveries later.
A study by Ambrose, Cox, and Yairi (1997) indicates that
recovering and persistent stuttering may, partly, represent different
subtypes. The frequency of persistent or recovered stuttering was
investigated in relatives to 66 stuttering children. The analysis of the
data pointed to the existence of two types of genes linked to stuttering:
one type increasing the risk of transient childhood stuttering, and
another type increasing the risk of persistent stuttering. The effects of
these two types of genes seemed to be additive. This additive effect
suggests that the genes affect the same cerebral system in the same
direction. When analyzing possible causes of stuttering it is important to
consider that stuttering in adults may be regarded as a subgroup of
stuttering, and that the causal factors in adults may be different from the
causal factors in the majority of young stuttering children. It may be the
case, for example, that persistent stuttering involves a higher frequency
of structural abnormalities.
An interesting finding regarding language development in
stuttering children was reported by Watkins, Yairi, and Ambrose (1999).
In the group of stuttering preschool children in the study summarized
above (Yairi & Ambrose, 1999) their expressive language abilities were
measured. The group with early onset stuttering, who entered the study
at age 2 to 3, showed syntactic abilities and length of utterances well
above what was expected for their age. In fact, in some aspects the
language abilities in this group were on a level with the norms for two
years older children. This was true both for children who recovered and
for children who persisted to stutter. Children who entered the study at a
later age showed language abilities at about age expectations, except for
the group of children with persistent stuttering in the oldest age group
(entering the study at age 4 to 5), whose abilities were somewhat below
the norm. These results indicate that children with early onset stuttering
tend to show precocious learning of language.
Stuttering and the Basal Ganglia 22
9.2. Aging and stuttering
There is a paucity of research regarding the effect of aging on the
severity of stuttering, but two small studies have been published.
Shames and Beams (1956) sent survey forms to priests, with questions
about the age and number of stuttering persons in their parish. The result
suggested a drop in the prevalence of stuttering persons after the age of
50. A similar trend was indicated in a small study by Kielska (2001).
9.3. Stuttering and cerebral degeneration or lesions
The review of "neurogenic stuttering" in Section 4 showed that
cerebral lesions can result in stuttering. Cerebral lesions or degeneration
can also, however, have the opposite effect, changing lifelong stuttering
to fluent speech. These paradoxical cases may provide important clues
regarding the mechanisms of stuttering. At least four reports of this type
have been published (Jones, 1966; Helm-Estabrooks, Yeo, Geschwind,
& Freedman, 1986; Miller, 1985; Muroi et al., 1999). For example, the
report by Miller (1985) described two persons with onset of severe
stuttering in childhood, whose stuttering disappeared when they
developed symptoms of progressive multiple sclerosis. As a further
example, the author of this paper has interviewed a man who claimed
that his stuttering was greatly and permanently improved after he
recovered from a robbery which caused head injury. He said that he was
very grateful to the robbers.
The disappearance of stuttering after cerebral lesions has been
interpreted as support for the hypothesis that stuttering is the
consequence of interference between the hemispheres, so that the lesion
dissolved the conflict (Jones, 1966). An alternative interpretation, based
on the discussion of dystonia in Section 7, could be that the lesions
resulted in a decrease of gain in cerebral circuits involved in speech. All
four cases reported by Jones (1966) showed bilateral speech
representation before surgery, changing to unilateral afterwards.
Bilateral speech representation might imply increased gain of speech
related signals in both hemispheres as a result of interhemispheric
connections between homologous cortical areas via the corpus callosum
(see discussion in Section 10.1, regarding increased interhemispheric
connections in symmetric brains). In this case the "hemispheric
interference" might be regarded as a variant of a more general
mechanism, namely overflow of speech related signals to the basal
ganglia circuits.
If most cases of stuttering are the result of excessive signals in
neural circuits, stuttering would be expected to improve in advanced age
since aging is related to many changes in the brain, for example
breakdown of myelin sheaths (Peters, 2002), leading to reduced
transmission of signals. The scarce reports of stuttering and aging
summarized above do support the hypothesis that stuttering often
improves at more advanced age. On the other hand, if most cases of
stuttering were the result of impaired processing capacity for speech,
then stuttering would be expected to become more severe by aging.
9.4. Summary of development and stuttering
The review above, of development, degeneration, etc., suggests a
pattern where the causal factors for stuttering are strongest around 2.5 to
3 years of age. The strength of these factors drops rapidly during the
preschool age in most cases. There is further decrease in late childhood
and adolescence, and also a tendency for diminishing of stuttering at an
advanced age. In some cases cerebral lesions or degeneration of white
matter result in normalization of speech. The causal factors are strongest
in males. An interesting finding is that children with early onset of
stuttering tend to show precocious language development.
9.5. Developmental changes of the nervous system
The summary in the previous section leads to the question: Are
there any developmental changes in the nervous system that follow this
time course, with a peak before age 3, rapid decrease in the preschool
years, slower decrease until adolescence, and further decrease in old
age? The development of the human nervous system continues after
birth, with major changes in many aspects during childhood (Webb,
Monk, & Nelson, 2001). Postmortem studies of synaptic density
(Huttenlocher, 1979; Huttenlocher & Dabholkar, 1997) and in vivo brain
imaging of cerebral metabolism (Chugani, 1999) indicate a pattern
where the general level of synaptic density increases from birth to about
1 to 3.5 years of age (with earlier development of for example auditory
and visual cortex, and later for the frontal cortex). This high level forms
Stuttering and the Basal Ganglia 23
a plateau lasting until about 7 to 9 years of age, and reaches the adult
low level in late adolescence. Goldman-Rakic (1987) argued that the
timing of the peak level of synaptic density in the frontal cortex is
related to the time of development of expressive language abilities and
cognitive functions. The timing of the peak in synaptic density
corresponds well with the typical time for onset of stuttering, but the
plateau lasts longer than most cases of childhood stuttering. The bulk of
recovery seems to occur before the age of 5 (Yairi & Ambrose, 1992;
Månsson, 2000), while the plateau of high synaptic density lasts until
about 7 to 9 years.
However, another neurodevelopmental aspect fits better with the
time course of stuttering, namely the density of dopamine receptors in
the striatum. The striatal density of D1 and D2 receptors has been
measured postmortem by Seeman et al. (1987), in children and adults
from the general population. Figure 2 shows the density of D1 and D2
receptors in the putamen, and the D1/D2 ratio. Both D1 and D2 receptor
densities show a linear increase after birth up to a peak level at age 3 for
D1 and age 2 for D2 (the correlation between receptor density and age
during this phase of increase: .86 for D1 and .82 for D2). This pattern of
D1 and D2 receptor development, with a marked peak, has also been
shown in rats (Teicher, Andersen, & Hostetter, 1995). The density of D2
receptors falls rapidly after the peak, with about 38% reduction at age 5
compared with the peak level. The time course of D2 density
development is similar to the typical time course of onset and recovery
of stuttering. For the D1 receptor there is just one case reported between
3 and 20 years, but this case suggests a slower reduction of D1
receptors.
Could dopamine receptor development explain the gender
difference in stuttering? In Figure 2 both boys and girls show similar
peaks of D1 and D2 receptor density. However, when looking at the
D1/D2 ratio in children one sees a separation of males and females, with
lower ratio in boys. The number of cases is very small and there are
differences in age between the boys and girls, but the tendency is
theoretically interesting. In the previous sections a model of the basal
ganglia was discussed, based on the principle that the indirect pathway
maintains a diffuse background inhibition of impulses while the direct
pathway provides a focused cue for release of the correct motor pattern.
The balance between D1 and D2 receptor density may be crucial, since a
high level of D2 receptors is assumed to reduce the diffuse inhibition
from the indirect pathway, and a relatively low level of D1 receptors is
thought to result in weaker cues from the direct pathway. A consequence
of this model would be that a low D1/D2 ratio impairs the cues from the
basal ganglia to the SMA (through the direct pathway) and at the same
time increases the risk of unintentional movements (through reduced
inhibition based on the indirect pathway). Impaired cues may result in
difficulties in initiation of segments in a speech motor sequence. A
hypothesis based on this reasoning would be that a low D1/D2 ratio in
the putamen, in combination with a high D2 density, increases the risk
for stuttering.
The time course of D1 and D2 receptor density presented in
Figure 2 suggests how changes in the D1/D2 ratio may be related to
onset and recovery of stuttering. The density of D2 receptors peaks
earlier than the D1 receptors. This means that the D1/D2 ratio is low
when the D2 density peaks, but that the ratio will rise later since the D1
density continues to increase while the D2 density drops. This rise of the
D1/D2 ratio could have a direct relation to childhood recovery from
stuttering.
The level of striatal D2 receptors has been reported to have a
positive correlation with cognitive performance irrespective of age
(Volkow et al., 1998; Bäckman et al., 2000). Maybe early development
of a high level of D2 receptors is the key factor in the group of children
with early onset of stuttering and precocious language development.
(The density of D2 receptors in putamen has also been reported to show
a negative correlation with the temperamental traits "detachment"
(reflecting the need for distance vs. intimacy, r = -.68 in Farde,
Gustavsson, and Jonsson (1997) and r = -.50 in Breier et al. (1998)) and
"irritability" (r = -.51 in Farde et al.).)
A further indication for a relation between high D2 density and
stuttering comes from cases with Tourette syndrome (TS). Ludlow
(1993) reported that 45% of persons with TS stuttered as children. A
study of twins with TS found a very strong positive correlation (r = .99)
between the severity of TS symptoms and the level of D2 receptor
binding in the head of the caudate nucleus (Wolf et al., 1996).
Stuttering and the Basal Ganglia 24
Figure 2. Density of D1 and D2 receptors in the putamen, and D1/D2
ratio, based on postmortem data published by Seeman et al. (1987), from
244 cases in the general population. The sign • marks females and + marks
males. The regression lines are calculated for the rise, decline, and adult
periods. The correlation between receptor density and age during the rise
period was .86 for D1 and .82 for D2 receptors. Note that for some
individuals only D1 or D2 receptor density was measured, resulting in a
lower number of individuals in the D1/D2 ratio plot. (In 24 of the cases
the densities in the putamen were not measured, instead the figures were
estimated from the available values for the caudate nucleus. The
correlation between receptor density in the putamen and caudate nucleus
was .82 in this study.)
-------------------------------------------------------------
If a low D1/D2 ratio in combination with a high D2 density
increases the risk of stuttering, blockade of D2 receptors with for
example haloperidol would be expected to balance the system. As
discussed in Section 6, haloperidol is the medication that has the best
documented effect on stuttering, and haloperidol is characterized by its
high specificity for D2 receptors. Studies of D2-blockers in stuttering
children are scarce, but the largest study (Gattuso & Leocata, 1962),
involving 50 children aged between 5 and 12, reported positive effects,
especially in the younger children (aged 5 to 8) compared with the older
ones. This is in line with the suggestion that increased D2 density is a
more important factor in early childhood stuttering compared with
stuttering in later age.
Another report discussed in Section 6 (Fish & Bowling, 1962)
claimed that amphetamine led to improvement of stuttering lasting a
long time after the medication was discontinued. Against this
background it is interesting that amphetamine has been shown to give a
long-lasting reduction in available D1 and D2 receptors in the striatum,
as a result of the receptors being internalized into the cytoplasm
(Dumartin, Caille, Gonon, & Bloch, 1998; Ginovart, Farde, Halldin, &
Swahn, 1999; Sun, Ginovart, Ko, Seeman, & Kapur, 2003). It does not
seem clear if the D1 and D2 receptors are affected to the same extent,
there are some indications for a stronger effect on the D2 receptor type
(Gifford et al., 2000). According to the suggested hypothesis of a
relation between stuttering and high D2 density in the putamen, this
Stuttering and the Basal Ganglia 25
mechanism would tend to reduce stuttering. This example shows that the
pharmacological effects in stuttering might be very complex and
sometimes paradoxical.
Another aspect of the basal ganglia that may be related to
developmental changes is the level of the enzyme tyrosine hydroxylase
(TH), which is the rate-limiting factor in the synthesis of dopamine
(Feldman et al., 1997). McGeer and McGeer (1976) reported a
pronounced elevation of the TH level in the putamen in the early
childhood, falling rapidly to adult levels in adolescence. This would
suggest an elevation of dopamine production in children. This pattern of
TH level was not, however, found in a similar study by Robinson et al.
(1977).
10. Anomalies of the cerebral cortex and possible relations to the
basal ganglia
The review in this paper is focused on the basal ganglia system,
but the functions of the basal ganglia are dependent on the functions of
the cerebral cortex and the white matter connections. Some of the most
interesting findings about persistent stuttering during recent years relate
to the morphology of the cortex and the structure of the underlying
white matter. Therefore a discussion of these anomalies will be included
here.
10.1. Increased area of planum temporale
Foundas et al. (2001) used magnetic resonance imaging (MRI) to
investigate cerebral morphology in 16 adults with persistent
developmental stuttering and 16 matched controls. There was no
reported history of brain injury, dyslexia, specific language impairment,
ADHD, or other neuropsychiatric disorders. The mean level of
education was high, 16.5 years. Half of the stuttering group had a family
history of stuttering. Two main findings of the study were: (a) increased
total size of the planum temporale (PT), and (b) increased number of
gyri in speech related areas in the stuttering group.
In the stuttering group the left PT was found to be in average 23%
larger and the right 30% larger, compared with the controls. An
interesting result was that the standard deviation of the PT size was
lower in the stuttering group. If calculating the standard deviation in
percent of the mean size for each group, the controls had 55% higher
standard deviation for the left PT and 73% higher for the right,
compared with the stuttering group. This indicates that large size of PT,
especially in the right hemisphere, was typical for the stuttering
individuals.
On average, the control group showed an asymmetry of the PT,
with larger left side. The persons who stuttered showed a more
symmetric pattern. It seems unlikely, however, that the lateralization in
itself would be a causal factor since the groups largely overlapped, with
about 30% of the controls showing an approximately symmetric
configuration and about 25% having a clearly larger right PT. The
difference in total PT size might be a more distinctive group difference
than the difference in asymmetry.
The characteristics of variations in PT size were discussed by
Rosen, Sherman, and Galaburda (1992). Based on a study of 100 human
postmortem brains they found that the degree of symmetry correlated
with the size of the smaller PT but not with the larger PT. In other
words, symmetric brains tend to have a large total PT area. Studies with
rats indicated that the sizes of cortical areas mainly are determined by
early events in the corticogenesis, in the progenitor cell stage, and that
symmetric areas tend to have a greater number of connections through
the corpus callosum.
Foundas et al. (2003) reported that delayed auditory feedback
(DAF) had the strongest fluency-inducing effect in the subgroup of
stuttering persons with rightward PT asymmetry. Was this also the
subgroup with the largest total PT area? As discussed in Section 7.6 the
effect of altered auditory feedback might be related to excessive gain in
auditory feedback loops. If this suggestion is correct, the total area of the
PT might be a factor that influences this feedback gain.
10.2. Increased gyrification
In the study by Foundas et al. (2001), discussed in the previous
section, 10 of 16 stuttering persons showed extra gyri along the superior
bank of the lateral sulcus (3 persons bilateral, 3 left, 4 right (note, error
in the original article, A. L. Foundas, personal communication, August
28, 2002)). None of the controls had extra gyri here. This region
Stuttering and the Basal Ganglia 26
includes speech related areas, like Broca's area and the sensorimotor
cortex for the articulatory organs. Further, 7 of 16 stuttering persons
were found to have an extra diagonal sulcus in the posterior Broca's
area, BA44 (3 persons bilaterally, 2 left, 2 right), while none of the
controls showed this pattern. In fact, the left hemisphere diagonal sulcus
was absent in 6 of the controls but only in 3 of the stuttering persons,
making a grand total of 18 left side diagonal sulci in stuttering persons
compared with 10 among the controls.
When reviewing the literature it turns out that regional increased
gyrification has been found in other language disorders. Increased
prevalence of extra gyri in the posterior part of the superior bank of the
lateral sulcus has been reported in both developmental language disorder
and dyslexia. In the general population about 10% of hemispheres show
this type of extra gyrus (Steinmetz, Ebeling, Huang, & Kahn, 1990).
Jackson and Plante (1996) found this extra gyri in 41% of 80
hemispheres in families with language disorder, while the control group
showed extra gyri in 22.5% of the hemispheres. Leonard et al. (1993)
reported extra gyri with this location in 6 of 9 adults with dyslexia, in 4
of 10 relatives, but in only 1 of 12 controls. Furthermore, 4 of these 9
cases with dyslexia had an extra Heschl's gyrus (auditory cortex), but
none of the 12 controls showed this pattern.
An increased number of gyri can be a sign of a developmental
disorder called polymicrogyria, with clearly disturbed structure of
cortical layers. It is often regional and is suggested to be the result of a
focal perfusion failure about the 6th month of gestation. The symptoms
are very varied, including epilepsy, spastic paresis, and mental
retardation, but there are also cases with only selective impairment of
higher functions (Guerrini, Canapicchi, & Dobyns, 1999). There seem to
be no reports of polymicrogyria in developmental stuttering.
10.3. Somatosensory white matter disturbance
Sommer, Koch, Paulus, Weiller, and Büchel (2002) used a type of
magnetic resonance imaging, diffusion tensor, to investigate the
microstructure of the white matter in adults with persistent
developmental stuttering. This method measures the anisotropy, an
index of differences of water diffusion in three dimensions. The
anisotropy is increased in white matter with a high degree of
myelination and high coherence of the orientation of the axons.
The study found that the stuttering group showed reduced
anisotropy in a region underlying the left sensorimotor representation of
the oropharynx in the superior bank of the lateral sulcus. Increased
gyrification in the superior bank of the lateral sulcus was reported by
Foundas et al. (2001), as discussed above. It seems possible that these
results are associated, with disorganized structure of the sensorimotor
region related to the speech organs in some persons with persistent
stuttering. (It would be important, however, to replicate the investigation
with diffusion tensor, since Sommer et al. (2002) make the reservation
that large voxel size in the study could result in influence of the gray-
white border. If the stuttering group had increased gyrification in this
region, the risk for gray matter influence might be higher in this group.)
If a dysfunction in the cortical sensorimotor region of the
oropharynx is associated with stuttering, could this finding be integrated
with the hypothesis that stuttering is related to a dysfunction of the basal
ganglia circuits? At the current state of knowledge any model will be
clearly speculative, but just as examples two models will be sketched.
The first suggestion is based on the principle that when a motor
sequence is executed the striatum receives continuous information from
the primary motor cortex (M1) about the output of the motor signals to
the muscles. It is likely that this continuous input to the striatum is used
as a basis for the basal ganglia to generate the cue for shifting to the next
motor segment (see discussion in Section 3.6). If the signal from the M1
to the striatum is too weak or distorted the generation of the shift-cue
may fail. The speech sequence becomes disrupted, resulting in repetition
of the previous segment. The second suggestion is that the balance
between auditory and somatosensory input to the basal ganglia may be
important for a normal function of the speech automaticity. If the
auditory input is strong and the somatosensory input is weak the system
might become unstable.
11. Conclusions
The following tentative conclusions are proposed, with the
intention of suggesting pathways for further research.
(a) There are strong indications that the basal ganglia-
Stuttering and the Basal Ganglia 27
thalamocortical motor circuit, through the putamen to the SMA, plays an
important role in the pathophysiology of stuttering. The dysfunction
may have various causes and may be the effect of interaction between
several factors. Possible factors might be, for example: high density of
D2 receptors and low D1/D2 ratio in the putamen; aberrant levels of
dopamine release; and focal lesions of the basal ganglia thalamocortical
circuit.
(b) The core dysfunction in stuttering is suggested to be impaired
ability of the basal ganglia to produce timing cues. Some of the
conditions that temporarily alleviate stuttering are proposed to be
effective by providing compensatory timing information. This pertains
to the rhythm effect, chorus speech, and singing. The adaptation effect is
mainly based on an improvement of the basal ganglia timing cues
resulting from practice of a specific speech sequence.
(c) Other conditions that tend to alleviate stuttering are suggested
to be effective because of de-automatization of the speech control. This
would apply to novel modes of speaking and to masked or frequency
altered auditory feedback. The effect of altered auditory feedback might
also be related to attenuation of the effective feedback signal.
(d) Influence of emotions and stress on stuttering is well
compatible with the suggestion of stuttering as a basal ganglia disorder.
(e) Concomitant symptoms, such as involuntary movements, are
thought to be the result of specific mechanisms related to the basal
ganglia circuits, prevalent in some but not in all cases of stuttering.
(f) A morphological study suggests the importance of cerebral
cortex anomalies in persistent stuttering, possibly in interaction with the
basal ganglia functions.
(g) The typical pattern of early childhood onset of stuttering and
subsequent recovery in many cases is proposed to be related to a peak in
D2 receptor density in the putamen about the age of 2 to 3, in
combination with a relatively low D1/D2 ratio in some children,
especially boys. This factor is suggested to be particularly important in
stuttering children with precocious language development.
(h) Stuttering is a heterogeneous disorder and characterization of
subtypes is an important task for research. Based on differential traits
(Van Riper, 1982; Daly, 1996), and differential responses to medication
(Langova & Moravek, 1964) two preliminary subtypes are suggested (it
should be noticed that the proposed differential pharmacologic effects
are based on very few cases):
Stuttering type 1: This group corresponds to what Daly (1996)
defined as "stuttering" (as opposed to "stuttering-cluttering") and is
similar to Van Riper's Track I and III (Van Riper, 1982), and may
constitute the majority of persons who stutter. There are some
indications that the speech in this subgroup tends to improve on
dopamine stimulants and to get worse on D2-blockers (it is too early,
however, to draw any conclusions about dopamine stimulants in the
treatment of stuttering). The onset of stuttering occurs after a period of
fluent speech, and tense speech initiation blocks often become an
important part of the problem. The stuttering tends to get worse in
relation to negative emotional reactions.
Stuttering type 2: This group corresponds to what has been called
"stuttering-cluttering" (Daly, 1996) and is similar to Van Riper's Track
II (Van Riper, 1982). There are indications that the stuttering tends to
improve on D2-blockers and to get worse on dopamine stimulants.
Frequent behavioral traits may be increased behavioral activation, high
speech rate, and talkativeness.
Acknowledgements
The preparation of this article has been supported by grants from the
Bank of Sweden Tercentenary Foundation, the Swedish Council for
Research in the Humanities and Social Sciences, the Royal
Physiographic Society, and the Sjöbring foundation. I want to thank Jarl
Risberg, Sven Jönsson and Rolf Öhman for valuable advice, information
and review of manuscript, Martin Ingvar, Ingmar Rosén, and Jimmy
Jensen for information, Peter Jönsson and Marianne Ors for review of
manuscript, Robert George Dewsnap for linguistic review, and Ehud
Yairi and Audrey Holland for important suggestions as reviewers for the
journal.
Stuttering and the Basal Ganglia 28
Appendix A. Continuing education
1. The circuits through the basal ganglia are organized in the
following way: The basal ganglia system receives its main input
from
(a) the brain stem. The output from the BG interacts closely with
the cerebellum.
(b) the frontal lobe. The output from the BG modulates the
activity of the entire cerebral cortex.
(c) the cerebellum. The output from the BG modulates the limbic
system.
(d) almost the entire cortex. The output from the BG modulates
the activity of the frontal lobe and parts of the brain stem.
(e) the limbic system. The output from the BG modulates the
auditory cortex.
2. The putamen can be described as
(a) the output nucleus of the basal ganglia, projecting to the
thalamus;
(b) a limbic structure, with key functions in emotional responses
like anxiety;
(c) the motor part of the striatum, which is the main input nucleus
of the basal ganglia system;
(d) a structure involved in the cognitive circuits of the basal
ganglia, important for syntactic aspects of speech;
(e) the auditory part of the basal ganglia.
3. According to the model of the basal ganglia presented in Section 2,
how do the direct and the indirect pathways interact to shape the
behavior?
(a) The direct and the indirect pathways amplify each other,
thereby selecting the desired response.
(b) The direct pathway provides a focused cue to the cerebral
cortex for the release of the desired behavioral program, while
the indirect pathway provide a diffuse background inhibition
of potentially competing responses.
(c) The direct pathway provides a constant inhibition of impulses,
while the indirect pathway acts as a noise filter, amplifying the
strongest cortical signals.
(d) The direct and indirect pathways are only important when
learning a new behavior, not when executing well-learned
movements.
(e) The direct pathway provides information about the muscular
tension, while the indirect pathway provides spatial
information.
4. What explanation of the effect of chorus speech to eliminate
stuttering is suggested in this paper? Chorus speech results in
(a) de-automatization of speech;
(b) reduced auditory feedback of the own voice;
(c) reduced anxiety;
(d) timing cues from the voice of the other person;
(e) a different and easier speech pattern.
5. The frequent pattern of early childhood onset and recovery of
stuttering is suggested to be related to
(a) a peak in synaptic density in the cerebral cortex during
childhood;
(b) increased density of D1 receptors in putamen in some children;
(c) a peak in the size of the planum temporale during childhood;
(d) a temporary right hemisphere dominance of the auditory
function during childhood;
(e) a peak in D2 receptor density in the putamen, in combination
with low D1/D2 ratio in some children.
Stuttering and the Basal Ganglia 29
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