Biology subjects

Dyke, K.

Publications and source records attributed to Dyke, K..

5 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

Temporally resolved glutamate and GABA responses measured in human medial frontal cortex during working memory encoding and recall

Resolving rapid neurochemical changes during cognition is key to linking neurophysiology with behaviour. We developed a mixed block/event-related design of a working memory (WM) task for functional magnetic resonance spectroscopy (fMRS) at 7T to resolve glutamate and GABA fluctuations during encoding and recall phases of WM. Participants performed the WM task interleaved with rest and control conditions while semi-LASER spectra were acquired from the medial frontal cortex. Group-level phase-specific analyses revealed significant glutamate, but not GABA, increases during encoding and recall relative to control. However, larger individual increases in GABA during encoding predicted higher WM accuracy. Glutamate exhibited distinct, temporally resolved peaks for encoding ([~]1.1s) and recall ([~]1.4s). These time courses extend beyond previously reported post-stimulus windows and align closely with behavioural response latencies. Our findings provide temporally high-resolved characterisations of glutamate responses during distinct phases of WM and highlight differential roles of glutamate and GABA in WM processes.

neuroscience↗

bioRxiv2024

Uncovering the Neural Correlates of the Urge-to-Blink: A Study Utilising Subjective Urge Ratings and Paradigm Free Mapping

Neuroimaging plays a significant role in understanding the neurophysiology of Tourette syndrome (TS), in particular the main symptom, tics, and the urges associated with them. Premonitory urge is thought to be a negative reinforcer of tic expression in TS. Tic expression during neuroimaging is most often required as an overt marker of increased urge-to-tic, which can lead to considerable head movement, and thus data loss. This study aims to identify the brain regions involved in urge in healthy subjects using multi-echo functional MRI and a timing- free approach to localise the BOLD response associated with the urge-to-act without information of when these events occur. Blink suppression is an analogous behaviour that can be expressed overtly in the MRI scanner which gives rise to an urge like those described by individuals with TS. We examined the urge-to-blink in 20 healthy volunteers with an experimental paradigm including two conditions, "Okay to blink" and "Suppress blinking", to identify brain regions involved in blink suppression. Multi-echo functional MRI data was analysed using a novel approach to investigate the BOLD signal correlated with the build-up of the urge-to-blink that participants continuously reported using a rollerball device. In addition, we used the method of multi-echo paradigm free mapping (MESPFM) to identify these regions without prior specification of task timings. Subjective urge scores were correlated with activity in the right posterior and ventral-anterior insula as well as the mid-cingulate and occipital cortices. Furthermore, blink suppression was associated with activation in the dorsolateral prefrontal cortex, cerebellum, right dorsal-anterior insula, mid-cingulate cortex and thalamus. These findings illustrate that different insula subregions contribute to the urge-for-action and suppression networks. The MESPFM approach showed co-activation of the right insula and cingulate cortex. The MESPFM activation maps showed the highest overlap with activation associated with blink suppression, as identified using general linear model analysis, demonstrating that activity associated with suppression can be determined without prior knowledge of task timings.

neuroscience↗

bioRxiv2024

Investigating neurometabolite changes in response to median nerve stimulation

BackgroundRhythmic median nerve stimulation (MNS) at 10Hz has been shown to cause a substantial reduction in tic frequency in individuals with Tourette Syndrome. The mechanism of action is currently unknown, but is hypothesised to involve entrainment of oscillations within the sensorimotor cortex. ObjectiveWe used functional magnetic resonance spectroscopy (fMRS) to explore the dynamic effects of MNS on neurometabolite concentrations. MethodsHere, we investigated the effects of rhythmic and arrhythmic 10Hz MNS on glutamate (Glu) and GABA concentrations in the contralateral sensorimotor cortex in 15 healthy controls, using a blocked fMRS design. We used a Mescher-Garwood-semi-localised by adiabatic selective refocusing (MEGA-sLASER) sequence at 7T. ResultsOur results show no difference in the difference-from-baseline measures between the two stimulation conditions. Looking at the effect of MNS over both conditions there is a trend for an initial increase in Glu/tCr (total creatine) followed by a decrease over time, whereas GABA/tCr decreased during each stimulation block. ConclusionThese results suggest that despite entrainment of oscillations during rhythmic MNS, there are no significant differences in the tonic neuromodulatory effects of rhythmic and arrhythmic stimulation. The reduction in glutamate over the course of stimulation may reflect a decrease in glutamatergic firing due to adaptation. This may make it less likely that an involuntary movement is generated during continuous stimulation.

neuroscience↗

bioRxiv2020

The role of the cingulate cortex in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome

Tourette syndrome (TS) is a neurological disorder of childhood onset that is characterised by the occurrence of motor and vocal tics. TS is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction and hyper-excitability of cortical limbic and motor regions that are thought to lead to the occurrence of tics. Individuals with TS often report that their tics are preceded by premonitory sensory/urge phenomena (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as a strong urge for motor discharge. While the precise role played by PU in the occurrence of tics is largely unknown, they are nonetheless of considerable theoretical and clinical importance as they form a core component of many behavioural therapies used in the treatment of tic disorders. Recent evidence indicates that the cingulate cortex may play an important role in the generation of PU in TS, and in urges-for-action more generally. In the current study we utilised voxel-based morphometry (VBM) techniques, together with seed-to-voxel structural covariance network (SCN) mapping, to investigate the putative role played by the cingulate cortex in the generation of motor tics and the experience of PU in a relatively large group of young people with TS. Whole-brain VBM analysis revealed that TS was associated with clusters of significantly reduced grey matter volumes bilaterally within: the orbito-frontal cortex; the cerebellum; and the anterior and mid cingulate cortex. Similarly, analysis of SCNs associated with bilateral mid- and anterior-cingulate seed regions demonstrated that TS is associated with increased structural covariance primarily with the bilateral motor cerebellum; the inferior frontal cortex; and the posterior cingulate cortex.

neuroscience↗