Saturday, October 29, 2011
Downregulation and Stuttering Treatments
A neural circuit may become desensitized to a drug through a process called downregulation. For example, benzodiazepines (BZs) bind to BZ receptors in the brain which are co-located with GABA-A receptors. BZ binding facilitates the binding of the GABA neurotransmitter to GABA-A receptors. Unfortunately, long term systematic use of BZs generally lead to neuro-adaptations resulting in the reduced binding of GABA (i.e., downregulation).
Similarly, dopamine receptors are typically stable, but sharp and prolonged increases in dopamine levels via stimulants can downregulate (i.e., reduce the numbers of) active dopamine receptors*. As a result of downregulation, drug tolerance increases and dosage escalation is necessary for the drug to maintain its effect.
A kind of downregulation may also be at play with various treatments aimed at alleviating stuttering. A stutterer might experience substantial gains in fluency during the early stages of a treatment but subsequently may regress into disfluent speech. For example, it is commonly reported by users of various delayed auditory feedback (DAF) devices, such as SpeechEasy, that these devices lose their effectivenesses with continued use.
It is not clear that such phenomena can be explained merely as a placebo effect or by the withdrawl of the moral support given by a therapist during the early stages of a treatment. Nor can these regressions into disfluency be explained by a subject’s possible lack of adherence to some strict protocol specified by the treatment. Instead, this diminishing effect over time, in some instances, might be due to an acclimatization or downregulation in the neural circuitry associated with a treatment.
DAF devices work by means of emulating choral speech, which has been recognized as a fluency inducing condition. One theoretical explanation of the effect of choral speech on fluency** is that the loop normally involved in spontaneous speech involving the basal ganglia (i.e., the medial premotor system) is preempted in favor of a downstream loop involving the cerebellum (i.e., the lateral premotor system; see blog post entitled “Stuttering and the Dual Premotor System”).
So it is puzzling as to why the impact of DAFs on fluency fade with time. Some sort of adaptation effects may come into play, but whether or not these adaptations involve neural circuitry downregulation is an open question. At any rate, the research literature is curiously absent of explanations concerning the fleeting effectivenesses of a variety of treatments for stuttering.
* It is interesting to speculate that the downregulation of dopamine receptors through the excessive use of amphetamines may lead to greater fluency in dopamine-sensitive stutterers by virtue of the fact that dopamine receptors are downregulated. However, this effect might only be temporary.
** Other explanations of the impact of DAFs on fluency revolve around impaired
auditory feedback and its impact on fluency.
Posted by stutter-mind-body at 11:58 AM