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1.
Neurobiol Lang (Camb) ; 5(2): 288-314, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38832358

RESUMO

Approximately 7% 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 a large cohort of 156 children and adolescents aged 10-16 years with a range of language abilities, including 54 with DLD, 28 with a history of speech-language difficulties who did not meet criteria for DLD, and 74 age-matched controls with typical language development (TD). We also examined cortical asymmetries in DLD using an automated surface-based technique. Relative to the TD group, 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. Analysis of the whole cohort using a language proficiency factor revealed that language ability correlated positively with surface area in similar regions. There were no differences in cortical thickness, nor in asymmetry of these cortical metrics between TD and DLD. 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.

2.
Biol Psychiatry Glob Open Sci ; 4(1): 363-373, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38298778

RESUMO

Background: Compulsive checking, a common symptom of obsessive-compulsive disorder (OCD), has been difficult to capture experimentally. Therefore, determination of its neural basis remains challenging despite some evidence suggesting that it is linked to dysfunction of cingulostriatal systems. This study introduces a novel experimental paradigm to measure excessive checking and its neurochemical correlates. Methods: Thirty-one patients with OCD and 29 healthy volunteers performed a decision-making task requiring them to decide whether 2 perceptually similar visual representations were the same or different under a high-uncertainty condition without feedback. Both groups underwent 7T magnetic resonance spectroscopy scans on the same day. Correlations between out-of-scanner experimental measures of checking and the glutamate/GABA (gamma-aminobutyric acid) ratio in the anterior cingulate cortex, supplementary motor area, and occipital cortex were assessed. Their relationship with subjective ratings of doubt, anxiety, and confidence was also investigated. Results: Patients with OCD exhibited excessive and dysfunctional checking, which was significantly correlated with changes in the glutamate/GABA ratio within the anterior cingulate cortex. No behavioral/neurochemical relationships were evident for either the supplementary motor area or occipital cortex. The excessive checking observed in patients was negatively correlated with their confidence levels and positively related to doubt, anxiety, and compulsivity traits. Conclusions: We conclude that experimental measures of excessive and dysfunctional checking in OCD, which have been linked to increased doubt, anxiety, and lack of confidence, are related to an imbalance between excitatory and inhibitory neural activity within the anterior cingulate cortex. This study adds to our understanding of the role of this region in OCD by providing a laboratory model of the possible development of compulsive checking.

3.
bioRxiv ; 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37503009

RESUMO

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 cerebellum's 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.

4.
Nat Commun ; 14(1): 3324, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37369695

RESUMO

There has been little analysis of neurochemical correlates of compulsive behaviour to illuminate its underlying neural mechanisms. We use 7-Tesla proton magnetic resonance spectroscopy (1H-MRS) to assess the balance of excitatory and inhibitory neurotransmission by measuring glutamate and GABA levels in anterior cingulate cortex (ACC) and supplementary motor area (SMA) of healthy volunteers and participants with Obsessive-Compulsive Disorder (OCD). Within the SMA, trait and clinical measures of compulsive behaviour are related to glutamate levels, whereas a behavioural index of habitual control correlates with the glutamate:GABA ratio. Participants with OCD also show the latter relationship in the ACC while exhibiting elevated glutamate and lower GABA levels in that region. This study highlights SMA mechanisms of habitual control relevant to compulsive behaviour, common to the healthy sub-clinical and OCD populations. The results also demonstrate additional involvement of anterior cingulate in the balance between goal-directed and habitual responding in OCD.


Assuntos
Ácido Glutâmico , Transtorno Obsessivo-Compulsivo , Humanos , Espectroscopia de Prótons por Ressonância Magnética , Comportamento Compulsivo , Ácido gama-Aminobutírico , Imageamento por Ressonância Magnética
5.
Elife ; 112022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36164824

RESUMO

Developmental 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 - multi-parameter 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) 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 Heschl's 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.


Seven percent of children struggle to learn their native language for no obvious reason. This condition is called Developmental Language Disorder (DLD). Children with DLD often have difficulty learning to read and write. They are at higher risk for academic underachievement and may struggle to find good jobs. Their language difficulties also contribute to difficulties making friends and emotional challenges. Scientists suspect children with DLD may have differences in areas deep in the brain that help people learn habits and rules. A new magnetic resonance imaging technique called multiparameter mapping (MPM) can help scientists determine if this is true. The technique measures the properties of brain tissue. It is particularly useful for measuring the amounts of a fatty protective sheath on brain cells called myelin. Myelin helps brain cells send information faster. Using MPM, Krishnan et al. show that children with DLD have less myelin in parts of the brain responsible for speaking, listening, and learning rules and habits. In the experiments, 56 children with typical language development and 33 children with DLD were scanned using MPM. Krishnan et al. then compared the two groups and found reduced myelin in these critical areas associated with learning a language in most of the children with DLD. But not all children with DLD had these differences. More studies are needed to determine if these brain differences cause language problems and how or if experiencing language difficulties could cause these changes in the brain. Further research may help scientists find new treatments that target these brain differences.


Assuntos
Imageamento por Ressonância Magnética , Bainha de Mielina , Núcleo Caudado , Criança , Substância Cinzenta , Humanos , Ferro , Imageamento por Ressonância Magnética/métodos
6.
J Speech Lang Hear Res ; 64(7): 2438-2452, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34157239

RESUMO

Purpose People who stutter (PWS) have more unstable speech motor systems than people who are typically fluent (PWTF). Here, we used real-time magnetic resonance imaging (MRI) of the vocal tract to assess variability and duration of movements of different articulators in PWS and PWTF during fluent speech production. Method The vocal tracts of 28 adults with moderate to severe stuttering and 20 PWTF were scanned using MRI while repeating simple and complex pseudowords. Midsagittal images of the vocal tract from lips to larynx were reconstructed at 33.3 frames per second. For each participant, we measured the variability and duration of movements across multiple repetitions of the pseudowords in three selected articulators: the lips, tongue body, and velum. Results PWS showed significantly greater speech movement variability than PWTF during fluent repetitions of pseudowords. The group difference was most evident for measurements of lip aperture using these stimuli, as reported previously, but here, we report that movements of the tongue body and velum were also affected during the same utterances. Variability was not affected by phonological complexity. Speech movement variability was unrelated to stuttering severity within the PWS group. PWS also showed longer speech movement durations relative to PWTF for fluent repetitions of multisyllabic pseudowords, and this group difference was even more evident as complexity increased. Conclusions Using real-time MRI of the vocal tract, we found that PWS produced more variable movements than PWTF even during fluent productions of simple pseudowords. PWS also took longer to produce multisyllabic words relative to PWTF, particularly when words were more complex. This indicates general, trait-level differences in the control of the articulators between PWS and PWTF. Supplemental Material https://doi.org/10.23641/asha.14782092.


Assuntos
Fala , Gagueira , Adulto , Humanos , Imageamento por Ressonância Magnética , Movimento , Medida da Produção da Fala , Gagueira/diagnóstico por imagem
7.
Neuroimage ; 226: 117599, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33285329

RESUMO

Developmental language disorder (DLD) is characterised by difficulties in learning one's native language for no apparent reason. These language difficulties occur in 7% of children and are known to limit future academic and social achievement. Our understanding of the brain abnormalities associated with DLD is limited. Here, we used a simple four-minute verb generation task (children saw a picture of an object and were instructed to say an action that goes with that object) to test children between the ages of 10-15 years (DLD N = 50, typically developing N = 67). We also tested 26 children with poor language ability who did not meet our criteria for DLD. Contrary to our registered predictions, we found that children with DLD did not have (i) reduced activity in language relevant regions such as the left inferior frontal cortex; (ii) dysfunctional striatal activity during overt production; or (iii) a reduction in left-lateralised activity in frontal cortex. Indeed, performance of this simple language task evoked activity in children with DLD in the same regions and to a similar level as in typically developing children. Consistent with previous reports, we found sub-threshold group differences in the left inferior frontal gyrus and caudate nuclei, but only when analysis was limited to a subsample of the DLD group (N = 14) who had the poorest performance on the task. Additionally, we used a two-factor model to capture variation in all children studied (N = 143) on a range of neuropsychological tests and found that these language and verbal memory factors correlated with activity in different brain regions. Our findings indicate a lack of support for some neurological models of atypical language learning, such as the procedural deficit hypothesis or the atypical lateralization hypothesis, at least when using simple language tasks that children can perform. These results also emphasise the importance of controlling for and monitoring task performance.


Assuntos
Encéfalo/fisiopatologia , Transtornos do Desenvolvimento da Linguagem/fisiopatologia , Adolescente , Criança , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Idioma , Imageamento por Ressonância Magnética/métodos , Masculino
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