Stuttering: A Disorder of Energy Supply to Neurons?

Abstract

Stuttering is a disorder characterized by intermittent loss of volitional control of speech movements. This hypothesis and theory article focuses on the proposal that stuttering may be related to an impairment of the energy supply to neurons. Findings from electroencephalography (EEG), brain imaging, genetics, and biochemistry are reviewed: (1) Analyses of the EEG spectra at rest have repeatedly reported reduced power in the beta band, which is compatible with indications of reduced metabolism. (2) Studies of the absolute level of regional cerebral blood flow (rCBF) show conflicting findings, with two studies reporting reduced rCBF in the frontal lobe, and two studies, based on a different method, reporting no group differences. This contradiction has not yet been resolved. (3) The pattern of reduction in the studies reporting reduced rCBF corresponds to the regional pattern of the glycolytic index (GI; Vaishnavi et al., 2010). High regional GI indicates high reliance on non-oxidative metabolism, i.e., glycolysis. (4) Variants of the gene ARNT2 have been associated with stuttering. This gene is primarily expressed in the brain, with a pattern roughly corresponding to the pattern of regional GI. A central function of the ARNT2 protein is to act as one part of a sensor system indicating low levels of oxygen in brain tissue and to activate appropriate responses, including activation of glycolysis. (5) It has been established that genes related to the functions of the lysosomes are implicated in some cases of stuttering. It is possible that these gene variants result in a reduced peak rate of energy supply to neurons. (6) Lastly, there are indications of interactions between the metabolic system and the dopamine system: for example, it is known that acute hypoxia results in an elevated tonic level of dopamine in the synapses. Will mild chronic limitations of energy supply also result in elevated levels of dopamine? The indications of such interaction effects suggest that the metabolic theory of stuttering should be explored in parallel with the exploration of the dopaminergic theory.

Digital therapy to improve stuttering symptoms in patients with a deficit of spectral power in the EEG beta frequency band

“…Next, we demonstrate that auditory stimulation is resulting in a speech quality improvement. The effectiveness of β -range BB stimulation to improve speech quality in AWS agrees with earlier studies suggesting a link between β deficit and stuttering 6,25,41 . Moreover, our results suggest that there is a dose-effect relation of speech improvement on the increase of β power in speech centers.…”

“…Neurophysiology studies have offered a promise of actionable discoveries in stuttering causes. A number of studies showed that the activity in the EEG β spectrum range (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), which is commonly heightened in awake state and focused activities 4 , is reduced in individuals with stuttering (reviewed in 5 ). EEG and magnetoencephalographic (MEG) studies have shown that in adults who stutter (AWS), as compared to the control group, α power is higher 5,6 while β power is lower during speech production 6 .…”

“…A number of studies showed that the activity in the EEG β spectrum range (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), which is commonly heightened in awake state and focused activities 4 , is reduced in individuals with stuttering (reviewed in 5 ). EEG and magnetoencephalographic (MEG) studies have shown that in adults who stutter (AWS), as compared to the control group, α power is higher 5,6 while β power is lower during speech production 6 . This may be due to the role of β band in coordinating speech planning and execution within the speech-production brain network, as it is known that β oscillations become more coherent between the bilateral primary motor, premotor, and auditory cortices before speech production 7 .…”

Source Localization and Spectrum Analyzing of EEG in Stuttering State upon Dysfluent Utterances

“…On the other hand, Alm proposed that reduced beta power at rest in AWS could be an indicator of limited neuronal supply that, through a direct effect, may result in stuttering by the reduction of neuronal firing frequency in the motor speech system. 10 In our opinion, the increased alpha and beta power over motor areas through SP for dysfluent utterances is arduous to explain with the hypothesis of neuronal firing deficiency. Moreover, increased delta band frequency has been associated with fluency, whereas in decreased metabolic rate, low band frequencies are empowered.…”

“…He proposed 2 ways in which a reduced supply of energy results in stuttering. 10 In direct effect theory, stuttering is caused by a reduced rate of firing by energy-deprived neurons involved in speech production. Moreover, he suggested an indirect effect hypothesis wherein metabolic impairments cause an elevated tonic level of synaptic dopamine, which, in turn, results in stuttering.…”