Biology subjects

Worbe, Y.

Publications and source records attributed to Worbe, Y..

3 recordsLinked to original sources

bioRxiv2026

Developmental delay in attaining adult levels of motor excitability in children and adolescents with Tourette syndrome: a mega-analysis study

Tourette syndrome (TS) is a neurodevelopmental disorder of childhood onset characterised by vocal and motor tics and is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction. TS often follows a developmental time course in which tics become increasingly more controlled during adolescence. However, many individuals continue to have debilitating tics into adulthood. This indicates that there may be important differences between adults with TS for whom the clinical phenotype is more stable, and children and adolescents with the disorder who may be undergoing developmental neuroplastic changes linked to the reduction of their tics. Previous studies have used transcranial magnetic stimulation (TMS) to investigate changes in cortical motor excitability in individuals with TS, including measurement of resting motor threshold (RMT). However, the findings from these studies have been mixed, have varied between adult and child samples, and have often been based on small sample sizes. Here we report a multi-centre, mega-analytic, study in which RMT data collected from children and adults with TS at multiple research centres was pooled for analysis. Results confirmed that mean RMT was significantly increased in individuals with TS compared to neurotypical controls. However, this result can be explained by the more important findings that: (a) RMT for adults with TS did not differ from that of neurotypical adults; and (b) the rate that RMT decreases with age during childhood and adolescence is reduced in individuals with TS compared to controls. Thus, while neurotypical individuals reach an adult RMT level by ~12-13 years of age, individuals with TS are substantially delayed in doing so, and do not reach an adult RMT level until much later, at ~24 years of age. We conclude therefore that differences in measures of cortical excitability between children and adolescents with TS and chronologically age-matched neurotypical controls may likely reflect a developmental delay in the maturation of functional brain networks in individuals with TS, which may normalise with age.

neuroscience↗

bioRxiv2026

Functional cerebellar connectomes interfacing motor adaptation and reinforcement feedback

Motor adaptation is driven by sensory prediction errors, yet reinforcement feedback can alter the speed and retention of adaptive behaviors. The cerebellum is central in motor adaptation, but posterior lobules, especially Lobule VI (CB6) and Crus I (CBcrus1), also participate in reinforcement-related signaling. Serotoninergic and dopaminergic systems, key modulators of motivational processes, directly influence cerebellar activity. However, how these neuromodulatory systems contribute to cerebellar network organization and to reinforcement-based adaptation in humans remains unclear. We employed a multimodal framework (Receptor-Enriched Analysis of functional Connectivity by Targets; REACT) using PET-derived Serotonin/Dopamine Transporter (SERT/DAT) templates to enrich resting-state functional Magnetic Resonance Imaging (rs-fMRI). We estimated SERT- and DAT-enriched functional connectivity from CB6 and CBcrus1 within motor-adaptation and reinforcement-learning networks, and tested their correlations with performance in a visuomotor adaptation task completed under reward and punishment. Our findings show lobule-specific neuromodulatory organization within the cerebellum. CB6 exhibited predominantly DAT- and SERT-enriched connectivity with motor adaptation networks, while CBcrus1 showed stronger SERT-enriched communication extending to both motor and reinforcement networks. Crucially, distinct cerebello-cortical neuromodulatory networks predicted individual differences in adaptation rate. DAT-enriched CBcrus1 connectivity was linked to punishment-driven adaptation, whereas SERT-enriched cerebello-orbitofrontal connectivity predicted faster adaptation across both reward and punishment contingencies. Furthermore, we observed overlaps between SERT- and DAT-enriched networks in the medial orbitofrontal area for Crus I, which predicted retention following punishment, underscoring the role of convergent neuromodulation in stabilizing adapted movements. We conclude that partially segregated yet convergent cerebello-cortical networks support interactions between motor and motivational behaviors, with combined and opposing effects of serotonergic and dopaminergic neuromodulation accounting for the speed and retention of adaptive behaviors.

neuroscience↗

bioRxiv2021

Action inhibition revisited: a new method identifiescompromised reactive but intact proactive control inTourette disorder

Tourette disorder (TD) is characterized by tics, which are sudden repetitive involuntary movements or vocalizations. Deficits in inhibitory control in TD patients remain inconclusive from the traditional method of estimating the ability to stop an impending action, which requires careful interpretation of a parameter derived from race model. One possible explanation for these inconsistencies is that race models assumptions are often violated. Here, we used a pair of metrics derived from a recent alternative model to address why stopping performance in TD patients is unaffected by impairments in neural circuitry. These new metrics distinguish between proactive and reactive inhibitory control and estimate them separately. When these metrics were contrasted with healthy controls (HC), we identified robust deficits in reactive control in TD patients, but not in proactive control. The patient population exhibited difficulty in slowing down the speed of movement planning, which they compensated by their intact ability of procrastination. TEASERTourette disorder patients inhibit action by means of strategic postponement to compensate impaired slowness in preparation.

neuroscience↗