Elevated iron concentration in putamen and cortical speech motor network in developmental stuttering

Abstract

Theoretical accounts of developmental stuttering implicate dysfunctional cortico-striatal-thalamo-cortical motor loops through the putamen. However, the analysis of conventional MRI brain scans in individuals who stutter has failed to yield strong support for this theory in terms of reliable differences in the structure or function of the basal ganglia. Here, we performed quantitative mapping of brain tissue, which can be used to measure iron content alongside markers sensitive to myelin and thereby offers particular sensitivity to the measurement of iron-rich structures such as the basal ganglia. Analysis of these quantitative maps in 41 men and women who stutter and 32 individuals who are typically fluent revealed significant group differences in maps of R 2 *, indicative of higher iron content in individuals who stutter in the left putamen and in left hemisphere cortical regions important for speech motor control. Higher iron levels in brain tissue in individuals who stutter could reflect elevated dopamine levels or lysosomal dysfunction, both of which are implicated in stuttering. This study represents the first use of these quantitative measures in developmental stuttering and provides new evidence of microstructural differences in the basal ganglia and connected frontal cortical regions.

Quantitative MRI reveals differences in striatal myelin in children with DLD

“…R2* is also considered a measure of myelin, but the T2* contrast is particularly sensitive to iron, especially within the basal ganglia. Despite R2* differences being noted in adults with speech problems in the putamen and cortical speech motor network (developmental stuttering, Cler et al, 2021 ), and observed links between verbal memory and R2* in the ventral striatum ( Steiger et al, 2016 ), we did not see any evidence for R2* differences anywhere in the brain when comparing our TD and DLD groups.…”

“…A growing number of studies use these maps to understand brain–behaviour relationships ( Allen et al, 2017 ; Clark et al, 2020 ). Most recently, we have used MPMs and found elevated iron levels in the putamen and speech motor network in people who stutter ( Cler et al, 2021 ). However, this novel semiquantitative protocol has not yet been used to examine microstructure in children with neurodevelopmental disorders.…”

Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses

“…Several putamen metrics have been associated with executive function, including blood flow [ 66 ], structural atrophy [ 67 ], and functional connectivity [ 68 ]. Iron accumulation in the putamen has also been described in developmental stuttering [ 69 ] and CADASIL [ 70 ]. Although most studies of dietary iron and cognition have been in children or anaemic individuals, there is some evidence that high dietary iron associates with poorer cognition [ 71 ].…”

Impact of moderate alcohol consumption on brain iron and cognition: observational and genetic analyses

“…Several putamen metrics have been associated with executive function, including blood flow [60], structural atrophy [61] and functional connectivity [62]. Iron accumulation in the putamen has also been described in developmental stuttering [63] and CADASIL [64]. How iron deposition could result in cognitive deficits requires further investigation.…”