Biology subjects

Watkins, K. E.

Publications and source records attributed to Watkins, K. E..

At least 19 recordsLinked to original sources

bioRxiv2026

Neural correlates of novel word-form learning in developmental language disorder

Children with developmental language disorder (DLD) have persistent language learning difficulties and often perform poorly on pseudoword repetition, a task that probes phonological, memory, and speech-motor processes that support vocabulary acquisition. Research on the neural basis of pseudoword repetition in DLD is limited. We used whole-brain functional MRI (fMRI) to examine pseudoword repetition and repetition-based learning in 46 children with DLD (ages 10-15 years) and 71 age-matched children with typical language development. During scanning, children heard and repeated pseudowords paired with visual referents, allowing us to track learning-related changes in neural activity across repetitions. Repeated pseudoword production yielded comparable behavioural learning across groups, with faster productions by later repetitions. Post-scan, form-referent recognition was comparable across groups, whereas pseudoword repetition accuracy was lower in DLD. Pseudoword repetition engaged a distributed neural network, including inferior frontal cortex bilaterally (greater on the left), premotor and sensorimotor cortex, and posterior temporal and occipital regions. Group differences emerged primarily in regions where activity was task negative (i.e., below baseline or deactivated): lateral occipito-parietal cortex (posterior angular gyrus), medial parieto-occipital cortex (retrosplenial), and right posterior cingulate cortex. Learning-related decreases in activity were similar across groups, but region-of-interest analyses showed reduced leftward lateralisation of activity in inferior frontal gyrus in DLD. These findings suggest weaker disengagement of the default mode network during a linguistically demanding task in DLD. Although repetition-based pseudoword learning recruited similar neural mechanisms in both groups, these mechanisms may operate less efficiently in DLD, alongside reduced hemispheric specialisation in inferior frontal cortex. HighlightsO_LISimilar repetition-related neural attenuation across groups during pseudoword learning. C_LIO_LIReduced default-mode network suppression during pseudoword repetition in DLD. C_LIO_LIReduced left-hemisphere specialisation of inferior frontal cortex in DLD. C_LIO_LIRepetition-based learning in DLD supported by less efficient neural networks. C_LI

neuroscience↗

bioRxiv2026

Differences in dynamic motor selection in stuttering

Stuttering involves interruptions to the smooth flow of speech occurring mostly at syllable onset.1 Speech fluency is enhanced in people who stutter (PWS) by external timing cues.2 This has been taken to indicate that difficulties in the temporal organisation of action selection and initiation during speech contribute to stuttering.3 An important unanswered question is whether putative temporal coordination difficulties are specific to speech or generalise to other actions. Here, we examined the temporal organisation of hand action selection in PWS. Twenty PWS and twenty typically fluent speakers (TFS) underwent magnetoencephalography (MEG) recording while performing a visuomotor working-memory task that encouraged temporally specific selection, preparation, and shifts between hand actions. Lateralised sensorimotor mu/beta-frequency (8-30 Hz) activity modulation accompanying hand-action prioritisation was weaker in PWS than TFS. Strikingly, this effect was specific to a period of high uncertainty regarding which action to select and when. Despite these differences, lateralised mu/beta modulation was functionally related to reaction times in both groups and reaction times were well matched between PWS and TFS. The findings suggest a general disruption of temporal structuring of action selection and preparation in stuttering.

neuroscience↗

bioRxiv2026

Hierarchical Signatures of Language in the Human Brain

Language relies on a hierarchy of sensory and cognitive processes, yet how different levels of this hierarchy are supported by distinct neural architectures remains unclear. Here we show that semantic processing, compared with phonological processing, is associated with higher-level brain networks, as characterized by resting-state fMRI connectivity, in vivo measures of cortical myelin, and cortical types derived from a cytoarchitecture-defined reference atlas. These relationships were established using individualized ultra-high field fMRI in both English and French speakers leveraging a multi-session, multi-modal 7T MRI protocol including a language localizer. For comparison, we developed an artificial neural network, in which a representational hierarchy spontaneously emerged where phonological information was captured in earlier layers and semantic information in later layers. By integrating individualized functional mapping, neuroanatomical characterization and artificial intelligence, this study advances understanding of the neural basis of language and provides a framework for linking biological and artificial systems of communication. Significance StatementLanguage is widely described as hierarchical, yet how this functional organization is implemented in the brains biological architecture remains unclear. By combining ultra-high field, individualized neuroimaging with in vivo measures of cortical microstructure and large-scale connectivity, this study establishes a framework for linking distinct levels of linguistic computation to the brains structural and functional organization. Integrating these findings with artificial neural network modeling further reveals shared principles between biological and machine systems. Together, this work advances a biologically grounded account of language, bridges cognitive neuroscience and artificial intelligence, and provides a roadmap for understanding how complex cognition emerges from structured brain architecture.

neuroscience↗

bioRxiv2025

The staphylococcal type VII secretion system delays macrophage cell death through modulating multiple cell death pathways

The major human pathogen Staphylococcus aureus is a facultatively intracellular bacterium that can replicate and survive within a range of host cells including macrophages. While macrophage-mediated immune modulation is pivotal in S. aureus pathogenesis, bacterial manipulation of macrophage pathways remains poorly understood. The specialised type VII secretion system (T7SSb) is an important virulence-associated factor and immune modulator during staphylococcal infection, although, unlike its mycobacterial counterparts, its role in controlling staphylococcal-macrophage interactions remains unclear. Employing high-resolution time-lapse imaging, we demonstrated an induction of cell death corpses or pore-induced cellular traps (PITs) during S. aureus infection of macrophages in vitro, with a higher number of PITs forming in macrophages infected with S. aureus lacking EssC ({Delta}essC), a central T7SS transporter. Interestingly, {Delta}essC-infected macrophages displayed increased bacterial escape compared to wild type (WT)-infected cells, implicating a role for T7SS in delaying macrophage cell death. {Delta}essC-infected macrophages were also efferocytosed less compared to WT in vitro. We investigated the induction of cell death signalling markers in WT and {Delta}essC-infected macrophages and demonstrated that the T7SS delayed the induction of key cell death pathways, necroptosis and pyroptosis. A dual RNAseq analysis of WT- and {Delta}essC-infected macrophages further indicated a T7SS-dependent increase in ferroptosis later in infection, along with modulation of chemokines. We demonstrated that individual T7SS effectors, EsxA and EsxC, which were induced within macrophages, could individually delay macrophage cell death. Furthermore, in a murine skin infection model, we showed that effector and transporter mutants have distinct S. aureus infection outcomes. Our findings suggest for the first time a key role for T7SSb proteins in controlling macrophage cell death, which impacts staphylococcal survival within the host during infection. ImportanceStaphylococcus aureus is a major hospital and community associated pathogen which causes an array of infections. S. aureus can survive within immune cells, which may provide a niche for this pathogen to both persist and disseminate. Here we report a role for the staphylococcal type VII secretion system b, which secretes effectors that have been associated with bacterial virulence, in delaying macrophage cell death induced in response to this pathogen. T7SS functions through interfering with inflammatory cell death pathways, impacting the local cellular and immune environment. Our findings thus highlight a protective role for this system in macrophages, distinct to functions reported for the mycobacterial T7SS, and may implicate similar functions for T7SS proteins from related pathogens. Controlling macrophage cell death could be a critical mechanism by which S. aureus modulates the local immune responses, enabling its survival within the host,

microbiology↗

bioRxiv2025

Differences in brain activity during sentence repetition in people who stutter: a combined analysis of four fMRI studies

Our understanding of the neural correlates of developmental stuttering benefits from the use of functional MRI (fMRI) during speech production. Despite two decades of research, however, we have reached little consensus. In the current study, we analysed pooled fMRI data from four different studies that used the same sentence reading task and methodological approach. The combined sample included 56 adolescents and adults who stutter and 53 demographically matched typically fluent controls. A sparse-sampling design was used in each study, in which participants spoke during the silent period between measurements of brain activity. Sentence reading evoked activity in both groups across frontal and temporal regions bilaterally. At statistical thresholds corrected for family-wise error, there were no significant group differences. An uncorrected threshold was applied to explore group differences in areas previously identified in earlier fMRI studies on stuttering. People who stutter (PWS) showed greater activity compared with controls in right frontal pole, right anterior insula extending to frontal operculum, left planum temporale, and midbrain, at the level of red nucleus. In contrast, PWS showed lower activity in left superior frontal sulcus, subgenual medial prefrontal cortex, right anterior temporal lobe, and portions of inferior parietal lobe bilaterally including the angular gyrus on the left. Despite pooling data across multiple studies to achieve a relatively large sample, group differences in regions involved in speech-motor control only emerged at an uncorrected voxel-wise threshold. Some of these findings align with previous fMRI studies, such as increased activity in the right anterior insular cortex.

neuroscience↗

bioRxiv2024

No Evidence of Altered Language Laterality in People Who Stutter across Different Brain Imaging Studies of Speech and Language

A long-standing neurobiological explanation of stuttering is the incomplete cerebral dominance theory, which refers to competition between two hemispheres for "dominance" over handedness and speech, causing altered language lateralisation. Renewed interest in these ideas came from brain imaging findings in people who stutter (PWS) of increased activity in the right hemisphere during speech production or of shifts in activity from right to left when fluency increased. Here, we revisited this theory using functional MRI data from children and adults who stutter, and typically fluent speakers (119 participants in total) during four different speech and language tasks: overt sentence reading, overt picture description, covert sentence reading and covert auditory naming. Laterality indices (LIs) were calculated for the frontal and temporal lobes using the LI toolbox running in Statistical Parametric Mapping. We also repeated the analyses with more specific language regions, namely the pars opercularis (Brodmann Area 44) and pars triangularis (Brodmann Area 45). Laterality indices in PWS and typically fluent speakers (TFS) did not differ and Bayesian analyses provided moderate to anecdotal levels of support for the null hypothesis (i.e., no differences in laterality in PWS compared with TFS). The proportions of the PWS and TFS who were left lateralised or had atypical rightwards or bilateral lateralisation did not differ. We found no support for the theory that language laterality is reduced or differs in PWS compared with TFS.

neuroscience↗

bioRxiv2023

Approaches to measuring language lateralisation: an exploratory study comparing two fMRI methods and functional transcranial Doppler ultrasound

In this exploratory study we compare and contrast two methods for deriving a laterality index (LI) from functional magnetic resonance imaging (fMRI) data: the weighted bootstrapped mean from the widely-used Laterality Toolbox (toolbox method), and a novel method that uses subtraction of activations from homologous regions in left and right hemisphere to give an array of difference scores (mirror method). Data came from 31 individuals who had been selected to include a high proportion of people with atypical laterality when tested with functional transcranial Doppler ultrasound (fTCD), and who had fMRI data for two tasks, word generation and semantic matching, which were selected as likely to activate different brain regions. In general, the mirror method gave better agreement with fTCD laterality than the toolbox method, both for individual regions of interest, and for a large region corresponding to the middle cerebral artery. LI estimates from this method had much smaller CIs than those from the toolbox method; with the mirror method, most participants were reliably lateralised to left or right, whereas with the toolbox method, a higher proportion were categorised as bilateral (i.e. the CI for the LI spanned zero). Reasons for discrepancies between fMRI methods are discussed: one issue is that the toolbox method averages the LI across a wide range of thresholds. Furthermore, examination of task-related t-statistic maps from the two hemispheres showed that language lateralisation is evident in regions characterised by deactivation, and so key information may be lost by ignoring voxel activations below zero, as is done with conventional estimates of the LI.

neuroscience↗

bioRxiv2023

Differences in cortical surface area in developmental language disorder

Approximately seven per cent of children have developmental language disorder (DLD), a neurodevelopmental condition associated with persistent language learning difficulties without a known cause. Our understanding of the neurobiological basis of DLD is limited. Here, we used FreeSurfer to investigate cortical surface area and thickness in 54 children and adolescents with DLD and 74 age-matched controls aged 10-16 years. We also examined cortical asymmetries in DLD using an automated surface-based technique. Those with DLD showed smaller surface area bilaterally in the inferior frontal gyrus extending to the anterior insula, in the posterior temporal and ventral occipito-temporal cortex, and in portions of the anterior cingulate and superior frontal cortex. There were no differences in cortical thickness, nor in asymmetry of these cortical metrics. Post-hoc exploratory analyses revealed that surface area in the left fusiform and inferior frontal cortex related to childrens reading and non-word repetition scores, respectively. This study highlights the importance of distinguishing between surface area and cortical thickness in investigating the brain basis of neurodevelopmental disorders and suggests the development of cortical surface area to be of importance to DLD. Future longitudinal studies are required to understand the developmental trajectory of these cortical differences in DLD and how they relate to language maturation.

neuroscience↗

bioRxiv2023

Microstructural Properties of the Cerebellar Peduncles in Children with Developmental Language Disorder

Children with developmental language disorder (DLD) struggle to learn their native language for no apparent reason. While research on the neurobiological underpinnings of the disorder has focused on the role of cortico-striatal systems, little is known about the role of the cerebellum in DLD. Cortico-cerebellar circuits might be involved in the disorder as they contribute to complex sensorimotor skill learning, including the acquisition of spoken language. Here, we used diffusion-weighted imaging data from 77 typically developing and 54 children with DLD and performed probabilistic tractography to identify the cerebellums white matter tracts: the inferior, middle, and superior cerebellar peduncles. Children with DLD showed lower fractional anisotropy (FA) in the inferior cerebellar peduncles (ICP), fiber tracts that carry motor and sensory input via the inferior olive to the cerebellum. Lower FA in DLD was driven by lower axial diffusivity. Probing this further with more sophisticated modeling of diffusion data, we found higher orientation dispersion but no difference in neurite density in the ICP of DLD. Reduced FA is therefore unlikely to be reflecting microstructural differences in myelination in this tract, rather the organization of axons in these pathways is disrupted. ICP microstructure was not associated with language or motor coordination performance in our sample. We also found no differences in the middle and superior peduncles, the main pathways connecting the cerebellum with the cortex. To conclude, it is not cortico-cerebellar but atypical olivocerebellar white matter connections that characterize DLD and suggest the involvement of the olivocerebellar system in speech acquisition and development.

neuroscience↗

bioRxiv2021

Quantitative MRI reveals differences in striatal myelin in children with DLD

AbstractDevelopmental Language Disorder (DLD) is a common neurodevelopmental disorder characterised by receptive or expressive language difficulties or both. While theoretical frameworks and empirical studies support the idea that there may be neural correlates of DLD in frontostriatal loops, findings are inconsistent across studies. Here, we use a novel semiquantitative imaging protocol - multiparameter mapping (MPM) - to investigate microstructural neural differences in children with DLD. The MPM protocol allows us to reproducibly map specific indices of tissue microstructure. In 56 typically developing children and 33 children with DLD, we derived maps of: 1) longitudinal relaxation rate R1 (1/T1); 2) the transverse relaxation rate R2* (1/T2*); and 3) Magnetization Transfer Saturation (MTsat). R1 and MTsat predominantly index myelin, while R2* is sensitive to iron content. Children with DLD showed reductions in MTsat values in the caudate nucleus bilaterally, as well as in the left ventral sensorimotor cortex and Heschls gyrus. They also had globally lower R1 values. No group differences were noted in R2* maps. Differences in MTsat and R1 were coincident in the caudate nucleus bilaterally. These findings support our hypothesis of corticostriatal abnormalities in DLD and indicate abnormal levels of myelin in the dorsal striatum in children with DLD.

neuroscience↗

bioRxiv2020

An fMRI study of initiation and inhibition of manual responses in people who stutter

Developmental stuttering is a speech motor disorder characterised by difficulties initiating speech and frequent interruptions to the speech flow. Previous work suggests that people who stutter (PWS) have an overactive response suppression mechanism. Imaging studies of speech production in PWS consistently reveal greater activity of the right inferior frontal cortex, an area robustly implicated in inhibitory control of both manual and spoken responses. Here, we used a manual response version of the stop-signal task during fMRI to investigate neural differences related to response initiation and inhibition in PWS. Behaviourally, PWS were slower to respond to go stimuli than people who are typically fluent (PWTF), but there was no difference in stop-signal reaction time. Our fMRI results were consistent with these behavioural results. The fMRI analysis revealed the expected networks associated with manual response initiation and inhibition in both groups. However, all contrasts between the two groups were characterised by overactivity in PWS relative to PWTF. This overactivity was significantly different for the initiation of responses (i.e. the go trials) but not for response inhibition (i.e. the stop trials). One explanation of these results is that PWS are consistently in a heightened inhibition state, i.e. areas of the inhibition network are more active, generally. This interpretation is consistent with predictions from the global response suppression hypothesis.

neuroscience↗

bioRxiv2020

Asymmetry of auditory-motor speech processing is determined by language experience

Speech processing relies on interactions between auditory and motor systems and is asymmetrically organized in the human brain. The left auditory system is specialized for processing of phonemes, whereas the right is specialized for processing of pitch changes in speech that affect prosody. In speakers of tonal languages, however, processing of pitch (i.e., tone) changes that alter word meaning is left-lateralized. This indicates that linguistic function and language experience shape auditory speech processing asymmetries; their effect on auditory-motor speech processing remains unknown, however. Here, we investigated the asymmetry of motor contributions to auditory speech processing in speakers of tonal and non-tonal languages. We temporarily disrupted the left or right speech motor cortex using repetitive transcranial magnetic stimulation (rTMS) and measured the impact of these disruptions on auditory processing of phoneme and tone changes in sequences of syllables using electroencephalography (EEG). We found that disruption of the speech motor cortex in the left, but not the right hemisphere, impaired processing of phoneme changes in both language groups equally. In contrast, the effect of motor disruptions on processing of tone changes differed in tonal and non-tonal language groups: disruption of the left speech motor cortex significantly impaired processing of tone changes in tonal language speakers, whereas disruption of the right speech motor cortex modulated processing of tone changes in non-tonal speakers. We conclude that the contribution of the left and right speech motor cortex to auditory speech processing is determined by the functional role of the acoustic cues in the listeners native language. Significance StatementThe principles underlying hemispheric asymmetries of auditory speech processing remain debated. The asymmetry of auditory speech processing is affected by the low-level acoustic cues, but also by their linguistic function. By combining TMS and EEG, we investigated the asymmetry of motor contributions to auditory speech processing in tonal and non-tonal language speakers. For the first time, we provide causal evidence that auditory-motor speech processing asymmetries are shaped by the functional role of the acoustic cues in the listeners native language. The lateralised top-down motor influences are likely to affect asymmetry of speech processing in the auditory system.

neuroscience↗

bioRxiv2020

Morphological and functional variability in central and subcentral motor cortex of the human brain

There is a long-established link between anatomy and function in the somatomotor system in the mammalian cerebral cortex. The morphology of the central sulcus is predictive of the location of functional activation peaks relating to movement of different effectors in individuals. By contrast, morphological variation in the subcentral region and its relationship to function is, as yet, unknown. Investigating the subcentral region is particularly important in the context of speech, since control of the larynx during human speech production is related to activity in this region. Here, we examined the relationship between morphology in the central and subcentral region and the location of functional activity during movement of the hand, lips, tongue, and larynx at the individual participant level. We provide a systematic description of the sulcal patterns of the subcentral and adjacent opercular cortex, including the inter-individual variability in sulcal morphology. We show that, in the majority of participants, the anterior subcentral sulcus is not continuous, but consists of two distinct segments. A robust relationship between morphology of the central and subcentral sulcal segments and movement of different effectors is demonstrated. Inter-individual variability of underlying anatomy might thus explain previous inconsistent findings, in particular regarding the ventral larynx area in subcentral cortex. A surface registration based on sulcal labels indicated that such anatomical information can improve the alignment of functional data for group studies.

neuroscience↗

bioRxiv2020

Mapping human laryngeal motor cortex during vocalization

The representations of the articulators involved in human speech production are organized somatotopically in primary motor cortex. The neural representation of the larynx, however, remains debated. Both a dorsal and a ventral larynx representation have been previously described. It is unknown, however, whether both representations are located in primary motor cortex. Here, we mapped the motor representations of the human larynx using fMRI and characterized the cortical microstructure underlying the activated regions. We isolated brain activity related to laryngeal activity during vocalization while controlling for breathing. We also mapped the articulators (the lips and tongue) and the hand area. We found two separate activations during vocalization - a dorsal and a ventral larynx representation. Structural and quantitative neuroimaging revealed that myelin content and cortical thickness underlying the dorsal, but not the ventral larynx representation, are similar to those of other primary motor representations. This finding confirms that the dorsal larynx representation is located in primary motor cortex and that the ventral one is not. We further speculate that the location of the ventral larynx representation is in premotor cortex, as seen in other primates. It remains unclear, however, whether and how these two representations differentially contribute to laryngeal motor control.

neuroscience↗

bioRxiv2019

Transcranial Direct current stimulation does not modulate performance on a tongue twister task

BackgroundTDCS modulates cortical excitability in a polarity-specific way. When used in combination with a behavioural task, it can also alter performance. Previously, tDCS modulated the performance of older adults on a complex speech motor learning task, which involved repetition of tongue twisters [1]. ObjectiveWe aimed to replicate this finding in healthy young participants and to extend it by measuring tDCS-induced changes in motor excitability using transcranial magnetic stimulation and motor-evoked potentials elicited in the lips. MethodIn a double-blind randomized sham-controlled study, three groups of 20 participants received: 1) anodal tDCS to the left IFG/LipM1 and cathodal tDCS to the right hemisphere homologue; or 2) cathodal tDCS over the left and anodal over the right; or 3) sham stimulation. Participants heard and repeated tongue twisters and matched simple sentences before, during and 10 minutes after the stimulation. Motor excitability was measured before and immediately after the tDCS. ResultsThe improvement in performance of tongue twister repetition from baseline to after stimulation was significantly greater than for the simple sentences but did not differ among the three groups. Motor excitability significantly decreased to a small but similar extent across the three groups. ConclusionsTDCS did not modulate performance on a complex articulation task in healthy young adults. TDCS applied concurrently with task learning also failed to modulate motor excitability in expected ways. TDCS may be most effective in brains where brain function is sub-optimal due to age-related declines or pathology.

neuroscience↗

bioRxiv2019

Altered auditory feedback induces coupled changes in formant frequencies during speech production

Speaking is one of the most complicated motor behaviours, involving a large number of articulatory muscles which can move independently to command precise changes in speech acoustics. Here, we used real-time manipulations of speech feedback to test whether the acoustics of speech production (e.g. the formants) reflect independently controlled articulatory movements or combinations of movements. During repetitive productions of \"head, bed, dead\", either the first (F1) or the second formant (F2) of vowels was shifted and fed back to participants. We then examined whether changes in production in response to these alterations occurred for only the perturbed formant or both formants. In Experiment 1, our results showed that participants who received increased F1 feedback significantly decreased their F1 productions in compensation, but also significantly increased the frequency of their F2 productions. The combined F1-F2 change moved the utterances closer to a known pattern of speech production (i.e. the vowel category \"hid, bid, did\"). In Experiment 2, we further showed that a downshift in frequency of F2 feedback also induced significant compensatory changes in both the perturbed (F2) and the unperturbed formant (F1) that were in opposite directions. Taken together, the results demonstrate that a shift in auditory feedback of a single formant drives combined changes in related formants. The results suggest that, although formants can be controlled independently, the speech motor system may favour a strategy in which changes in formant production are coupled to maintain speech production within specific regions of the vowel space corresponding to existing speech-sound categories.\n\nNew & NoteworthyFindings from previous studies examining responses to altered auditory feedback are inconsistent with respect to the changes speakers make to their production. Speakers can compensate by specifically altering their production to offset the acoustic error in feedback. Alternatively, they may compensate by changing their speech production more globally to produce a speech sound closer to an existing category in their repertoire. Our study shows support for the latter strategy.

neuroscience↗

bioRxiv2019

Cross-species cortical alignment identifies different types of neuroanatomical reorganization in higher primates

Evolutionary modifications of the temporo-parietal cortex are considered to be a critical adaptation of the human brain. Cortical adaptations, however, can affect different aspects of brain architecture, including areal expansion or changes in connectivity profiles. We propose to distinguishing different types of brain reorganization using a computational neuroanatomy approach. We investigate the extent to which between-species alignment based on cortical myelin can predict changes in connectivity patterns across macaque, chimpanzee and human. We show that expansion and relocation of brain areas are sufficient to predict terminations of several white matter tracts in temporo-parietal cortex, including the middle and superior longitudinal fasciculus, but not of the arcuate fasciculus. This demonstrates that the arcuate fasciculus underwent additional evolutionary modifications affecting the connectivity pattern of the temporal lobe. The presented approach can flexibly be extended to include other features of cortical organization and other species, allowing direct tests of comparative hypotheses of brain organization.

neuroscience↗

bioRxiv2018

Transcranial direct current stimulation over left inferior frontal cortex improves speech fluency in adults who stutter

Stuttering is a neurodevelopmental disorder affecting 5% of children, and persisting in 1% of adults. Promoting lasting fluency improvement in adults who stutter is a particular challenge. Novel interventions to improve outcomes are required, therefore. Previous work in patients with acquired motor and language disorders reported enhanced benefits of behavioural therapies when paired with transcranial direct current stimulation (tDCS). Here, we report the results of the first trial investigating whether tDCS can improve speech fluency in adults who stutter. Thirty adult men who stutter completed a randomized, double-blind, controlled trial of anodal tDCS over left inferior frontal cortex. Fifteen men received 20 minutes of 1-mA tDCS on five consecutive days while speech fluency was temporarily induced using choral and metronome-timed speech. The other 15 men received the same speech fluency intervention with sham stimulation. We predicted that applying anodal tDCS to the left inferior frontal cortex during speech production with temporary fluency inducers would result in longer-lasting fluency improvements. Speech fluency during reading and conversation was assessed at baseline, before and after the stimulation on each day of the five-day intervention, and at 1 and 6 weeks after the end of the intervention. TDCS combined with speech fluency training significantly reduced the percentage of disfluent speech measured 1 week after the intervention compared with fluency intervention alone. At 6 weeks after the intervention, this improvement was maintained during reading but not during conversation. Outcome scores at both post-intervention time points on a clinical assessment tool (the Stuttering Severity Instrument - version 4) also showed significant improvement in the group receiving tDCS compared with the sham group, in whom fluency was unchanged from baseline. We conclude that tDCS combined with behavioural fluency intervention has the capacity to improve fluency in adults who stutter. tDCS thereby offers a potentially useful adjunct to future speech therapy interventions for this population, for whom therapy outcomes are currently limited.

neuroscience↗