Studies suggest the brain basis of stuttering


Much more than just common sense suggests a neurologic basis for stuttering, including studies using drugs and studies using brain imaging techniques such as PET scans and functional magnetic resonance imaging (fMRI).

The fact that various drugs have caused stuttering in some nonstutterers and various drugs appear to have decreased stuttering in some stutterers strongly suggests a neurologic basis.

Studies of drugs used to treat stuttering

Many drugs have been evaluated to see if they have a beneficial effect on developmental stuttering, but few studies have been adequately designed until those done in more recent years.

There are single case reports of beneficial effects on stuttering with the beta-blocker drugs propranolol and betaxolol.1,2 A study with the beta-blocker oxprenolol found no benefit. Beta-blockers are used primarily for high blood pressure and heartbeat disturbances. Because of their physiologic “calming” effects on the heart and body, they’ve been used for stage fright. Tournament target shooters have used them to diminish heartbeat force and fine hand tremors.

Haloperidol has been studied more than any other drug for its effects on stuttering. This drug’s primary use is for psychotic disorders such as schizophrenia. It’s also been used for Tourette’s disorder and severe behavioral problems in children.

One study reported that 31% of 26 patients with Tourette’s disorder stutter or had stuttered in the past.3

Many researchers have suggested that stuttering may be related to hyperactive dopaminergic systems in the brain. Dopamine is a chemical neurotransmitter. Haloperidol blocks dopamine receptors (more specifically, D-2 receptors), which reduces the effect of dopamine.

The results with haloperidol have been generally positive. It’s more effective than placebo (an inactive agent). Most stutterers, even those whose speech improves significantly on the drug, stop using it due to side effects.4

Haloperidol can cause extrapyramidal syndrome (EPS), characterized by Parkinson’s-like symptoms and abnormal movement disorders, including a mask-like (expressionless) face, drooling, tremors, rigidity, and shuffling gait.

Most studies of haloperidol on stuttering were done before the risk of tardive dyskinesia (TD) was fully appreciated. TD is a long term potential side effect of haloperidol and other such drugs. The condition may be irreversible, and is characterized by involuntary slow, rhythmical movements, especially of the mouth and tongue (“fly catching,” “lip smacking”), or constant blinking.

Verapamil is a calcium channel blocker primarily used for high blood pressure and heart disorders. In 1980, Zachariah reported on a patient whose stutter diminished when given verapamil for a heartbeat disturbance.5 On a follow-up study of 70 adult stutterers, he reported significant improvement with verapamil. However, the study format has been criticized.

A study by Brady and colleagues found only modest benefits. At a 6-month follow-up, only two of the original 10 patients remained on verapamil, though they reported virtually no side effects. The two patients who continued the drug were enthusiastic about its benefit.6

Yet another study found no evidence of improvement with verapamil.7 However, this study used a dose of 160 mg/day, while the Brady study used a larger dose of 240 mg/day, which might account for the apparent difference.

Brady and colleagues have also gotten results similar to verapamil with other calcium-blockers (nifedipine and diltiazem).

It’s hypothesized that verapamil might diminish stuttering by its calcium-blocking activity. When stimulated by signals from the brain, calcium is released at the neuromuscular junction. The calcium activates the muscle proteins actin and myosin, which in turn, cause muscles to move. However, speech production muscles are striated muscle (voluntary), and verapamil would be expected to exert a greater effect on smooth muscle (such as blood vessels).

It’s interesting to note, though, that haloperidol, like verapamil, has strong calcium blocking activity in addition to its effects on dopamine.8

Promising results have been reported with bethanecol, which increases the action of the neurotransmitter acetylcholine.9 One rationale for this is the fact that drugs which counter the action of acetylcholine, such as tricyclic antidepressants, have induced stuttering in some nonstutterers.

Clonidine is used primarily for high blood pressure. It has also been used for Tourette’s disorder, attention deficit hyperactivity disorder (ADHD) and autism.

One study with clonidine treatment for stuttering without Tourette’s disorder consisted of five boys aged 8-14 and two girls aged 9 and 15. Five children were observed by speech pathologists to show an obvious decrease in stuttering. The other two (13 and 14 years old) did not show a significant decrease in stuttering.10

Clonidine stimulates pre-synaptic alpha-2 adrenergic receptors. This reduces sympathetic outflow from the brain by inhibiting the release of the neurotransmitter norepinephrine.

More recently, psychiatrist and PWS Gerald Maguire has led pioneering research which suggests that dopamine overactivity may play a role in developmental stuttering. Studies have shown that atypical antipsychotics such as risperidone and olanzapine tend to reduce stuttering in persons who stutter. These drugs work by reducing dopamine activity in the brain.

Studies of drugs which have caused stuttering in nonstutterers

Overactivity of the neurotransmitter dopamine has been implicated as a possible factor in developmental stuttering. In rare cases, neural speech production systems in nonstutterers with “normal” dopamine activity might be thrown out of whack by drugs that affect dopamine (e.g., SSRIs, benzodiazepines, antipsychotics), while these same drugs might reduce stuttering in PWS who have “abnormal” dopamine activity.

There are reported cases of fluoxetine (Prozac) causing stuttering in nonstutterers. Fluoxetine (Prozac) is a selective serotonin reuptake inhibitor (SSRI) used for treating clinical depression, obsessive-compulsive disorder (OCD), and other conditions. SSRIs make more serotonin available in the brain by blocking its reuptake.

One woman taking fluoxetine started stuttering severely, requiring 3-5 tries to start most words. After stopping the drug, the stuttering resolved over the next two weeks, which parallels the time needed for fluoxetine to be eliminated from the body.

Alprazolam (Xanax), a benzodiazepine anti-anxiety agent and GABA agonist, also has been implicated in causing stuttering in a nonstutterer.

After taking alprazolam, a 22-year-old woman began stuttering severely. The stuttering ceased when the drug was stopped. The patient agreed to a double-blind, placebo-controlled trial. She stuttered severely on the two days she took alprazolam. The two days she took the placebo, there was no stutter. The researchers said the stuttering was not caused by anxiety, because the patient’s anxiety level was the same on all days of the trial, including the two days she did not stutter when on the placebo.

Some antipsychotics have been implicated in causing stuttering in nonstutterers. On the other hand, antipsychotics such as haloperidol and newer atypical antipsychotics such as risperidone and olanzapine have been used to reduce stuttering in PWS.

So it seems that drugs associated with reducing stuttering in persons who stutter might rarely have the opposite effect in nonstutterers. One thing to keep in mind is that the body strives to keep levels of neurotransmitters in balance. If the level or action of one neurotransmitter is altered, the body may alter the level or action of other neurotransmitters to keep a balance.

Stuttering has also been associated with the use of tricyclic antidepressants and phenothiazines (older antipsychotic agents).

Brain imaging studies continue to show differences in stutterers

A 1995 PET scan study by Fox and Ingham found that when nonstutterers spoke, brain activation was higher in the left hemisphere than in the right in areas that control the muscle movements necessary for speech–and also in the auditory areas that process incoming language formation. In stutterers, however, this dominance occurred in the right hemisphere. This difference persisted even during chorus reading (which induces fluency in most stutterers). This suggests an inherent difference in the way nonstutterers and stutterers process and output language.13

Ludlow and Braun of the National Institute of Deafness and Other Communication Disorders (NIDCD) have published similar findings. They also found that when stutterers speak, the left hemisphere language areas seem to be less active compared to nonstutterers even when stuttering is suppressed (e.g., by chorus reading). Ludlow said this means that we can’t look on stuttering as simply a motor-control disorder, but as a more fundamental disorder of the brain’s interface between language and speech. She said that recent findings lean her toward the idea that stuttering may be caused by the failure of the brain to develop normal left-hemispheric dominance for language.13

(This is certainly not a new idea, and I’ve been espousing this idea as a likely candidate for the cause of stuttering for decades. That is, that stutterers might have bilateral language areas (one in each brain hemisphere), in competition with each other, which causes a “bottleneck” in speech production. Signals to initiate speech are sent from two separate brain areas to speech articulator muscles at the same time. The speech articulator muscles need one dominant or consolidated set of signals, but are bombarded with two in stutterers. The greater the bottleneck, the more severe the speech block and stutter. As I’m fond of saying, words must get out of the brain before they can get out of the mouth.)

What this also suggests is that the even when a PWS is fluent, as many are when choral reading, speaking alone or to a pet, the neurologic flaw is still there. Many PWS and speech-language pathologists (SLPs) hold the misguided notion that this situational fluency experienced by PWS indicates that stuttering must be due to psychological or emotional causes. Such situational fluency indicates only that developmental stuttering is probably not caused by a lesion or overt damage as is neurogenic (acquired) stuttering, which tends not to show such variability. I believe that this situational fluency (the Primary Paradox) experienced by PWS can be explained by my excitation feedback component of stuttering, which may be due to a flaw in the brain’s limbic areas in PWS.

Ludlow goes on to say that these newer studies lend support to the view that speech therapy should start as soon as a child shows signs of stuttering. Treating the problem early, when language function may be more malleable, holds the best chance of actually influencing language development.

(I agree that a predisposition to develop chronic stuttering may be preventable in some cases if effective speech therapy is started early enough. I also happen to think that the neuropatterning techniques used in the Home Course are the most effective type of speech therapy. For kids, the techniques could be much simplified.)

Before the newer brain imaging studies came on the scene, two studies by Webster (1986, 1988) showed differences in bimanual handedness for stutterers compared to nonstutterers. This may reflect a conflict in inter-hemispheric communication expressed through tasks requiring the use of both hands. In 1986, Webster reported that distinct differences for stutterers while tapping with one hand and while at the same time doing another motor task with the other hand. In 1988, Webster used a task that required subjects to write letters bimanually. Stutterers wrote significantly more slowly than nonstutterers, made more mirror reversals of letters (particularly with the non-preferred hand), and showed poor quality of letter formation. In a 1989 study, Webster and Vaughn had similar findings, including the finding that nonstutterers were slightly more lateralized in handedness.18

In 1995, PET scan studies by Gerald Maguire (a psychiatrist at the University of California at Irvine and a PWS himself) and colleagues show that stuttering appears to be associated with decreased activity in several brain areas, including the left language circuit (Broca’s and Wernicke’s areas), higher order association areas (superior frontal cortex), right cerebellum, and the posterior cingulate (limbic system).14

Many of these areas become more activated (closer to normal function) when PWS are induced to be fluent (e.g., by chorus reading).

But a persistent defect is found in the left caudate nucleus during both fluent and stuttered speech in PWS.14 The caudate nucleus is part of the basal ganglia, which controls complex voluntary movements such as those required for speech. The left caudate nucleus does not function at full capacity even when a PWS is fluent, but at only about 40-50% of normal.

Maguire thinks that when a PWS speaks fluently, he may be using alternate speech production pathways (rather than the pathway for the usual stuttered speech). He says, “For instance, with chorus reading, delayed auditory feedback, the Edinburg Masker, or singing, I believe we’re bypassing that loop. Or somehow activating it just slightly.”15

The limbic system (posterior cingulate) is our emotional modulator. This is the brain area that controls what Maguire calls our “internal anxiety” level. He points out that this “internal” anxiety is not the same as the anxiety caused by external stresses such as asking for a raise or making an important speech. Our internal anxiety levels are not under voluntary control and we may not even be aware of them.

There’s an inverse relationship. The less active the limbic system, the higher the internal anxiety level. The more active the limbic system, the lower the internal anxiety level. During stuttered speech, the limbic system of PWS is less active, which indicates higher internal anxiety. During fluent speech (e.g., during chorus reading), the limbic system of PWS is more active, which indicates a lower internal anxiety.

Maguire’s “internal anxiety” is another term for my excitation feedback component of stuttering.

Another thing Maguire found is that the substantia nigra area in the brain is slightly overactive when PWS speak fluently when compared to nonstutterers. He postulates that this area might be overcompensating and bypassing the caudate nucleus defect somehow.

One of Dr. Maguire’s research projects involves the use of a newer drug called risperidone–similar to haloperidol–but with less potential to cause serious side effects. Like haloperidol, risperidone antagonizes the effect of dopamine. It’s thought that dopaminergic activity in certain brain areas may be too high in some PWS.

Maguire has also studied the effects of nimodipine on stuttering. Nimodipine is a calcium-blocker similar to verapamil, but with more specific effects in the brain. A third of PWS taking nimodipine showed improvement and none of the PWS on placebo (inactive agent) did. The findings suggest that nimodipine may be effective for some PWS, but further study is needed.

Maguire, commenting on the speculation by some researchers that calcium-blockers like verapamil and nimodipine work by stopping or easing tremors or spasms in the vocal cords, said “I know that stuttering is much more than just a spasm in the larynx. It’s not just one muscle group. It’s a coordination of all of it. It’s got to be in the brain.”15