Biology subjects

Jackson, S. R.

Publications and source records attributed to Jackson, S. R..

16 recordsLinked to original sources

bioRxiv2026

Exploring the beta burst dynamics of cued voluntary movements in Tourette Syndrome

Tourette Syndrome (TS) is a neurodevelopmental hyperkinetic disorder characterised by involuntary tics. These tics are thought to arise due to hyperexcitability of the motor cortex due to disinhibition within the cortico-striato-thalamo-cortical pathway. Given the involvement of motor circuits in this disorder, we explored whether there is a difference in the oscillatory dynamics of voluntary movements in people with tic disorders. We recorded optically pumped magnetometer magnetoencephalography during cued voluntary finger abductions in individuals with tic disorders and age- and sex-matched neurotypical controls. We analysed the data both using conventional time frequency analysis and using hidden Markov modelling to explore the difference in beta burst characteristics and dynamics. Whilst no differences were seen between groups during conventional analysis, we demonstrated an increase in beta burst duration during the post-movement beta rebound within the contralateral motor cortex in individuals with TS suggestive of increased inhibition following movement. We also show evidence of increased contralateral sensorimotor functional connectivity and reduced connectivity from and between frontal regions, as measured using coincident beta bursts. This is suggestive of disrupted functional connectivity within frontal control networks in individuals with TS.

neuroscience↗

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

Sensorimotor mapping of volitional facial movements in Tourette Syndrome

BackgroundTourette Syndrome (TS) is a neurodevelopmental movement disorder involving involuntary motor and vocal tics believed to be characterised by disordered neural inhibition. Cortical representations have previously been manipulated by disruptions in the inhibitory neurotransmitter {gamma}-aminobutyric acid (GABA). However, while facial tics are the most reported motor tic, it is unclear if facial sensorimotor representations differ in TS. MethodsSixteen individuals with Tourette Syndrome (TS) or chronic tic disorder and twenty typically developing (TD) control participants underwent 3-Tesla functional magnetic resonance imaging (fMRI). Blood-oxygenation level-dependent (BOLD) responses were measured during a block-design task comprising cued facial movements of common facial tics (blinking, grimacing and jaw clenching). Activations in bilateral pre- and post-central cortices and supplementary motor areas (SMA) were examined. Conjunction analyses identified voxels commonly and uniquely activated across movements within each group. ResultsBoth groups showed significant activations in the bilateral sensorimotor cortices and SMA in response to blink, grimace and jaw clench movements, with no significant between-group differences. Between-group similarities were lowest for unique blink maps. Common voxel maps also revealed low between-group similarity, with reduced sensorimotor activation and no shared SMA activation across movements in the TS group. ConclusionVoluntary facial sensorimotor representations do not differ between groups. However, low similarities between group unique blink maps may reflect greater prevalence of blinking tics in TS. Additionally, reduced overlap in sensorimotor activation and absent common SMA engagement across cued movements in the TS group may indicate altered motor integration or action initiation.

neuroscience↗

bioRxiv2026

Low-intensity sub-threshold rhythmic 10Hz median nerve stimulation modulates mu-band EEG oscillations in individuals with Tourette syndrome

Tourette syndrome (TS) is a neurological disorder characterised by the occurrence of vocal and motor tics. Rhythmic 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 has been hypothesised to involve entrainment of cortical oscillations within the sensorimotor cortex linked to the initiation of movement. An important methodological detail of these studies is that MNS is delivered at or above threshold (i.e., the minimum stimulation level required to elicit a visible muscle twitch). This is important issue as it means that the observed effects of rMNS could be driven primarily by afferent signals in response to stimulation, the re-afferent signals arising from the muscle, or a combination of these signals. To examine this further, we used electroencephalography (EEG) to investigate the effect of delivering 1s trains of sub-threshold rhythmic 10Hz MNS in a group of 15 adults with TS compared to a matched group of 20 neurotypical control participants. The results demonstrate that the EEG response (somatosensory evoked potential (SEP) to rMNS increased linearly with increasing stimulation amplitude. This was paralleled by substantially increased inter-trial coherence (ITC) during rMNS. Importantly, the duration of increased ITC was reduced for the TS group compared to controls. Importantly, these results were largely similar when analyses were restricted only to sub-threshold trials in which no visible muscle twitch was elicited by MNS. These results confirm that sub-threshold rhythmic MNS is sufficient to modulate somatosensory physiology and may also be sufficient to elicit the clinical benefits previously observed for MNS.

neuroscience↗

bioRxiv2025

Disrupting action control with transcranial ultrasound neuromodulation: a step forward for Tourette syndrome

BackgroundWhile Tourette syndrome (TS) is characterised by the presence of tics, premonitory urges are involved in both triggering them and as a lever to control them. The right insular cortex is known to play a key role in these processes, yet its precise functional contribution remains unclear. Transcranial ultrasound stimulation (TUS) is currently one of the only non-invasive neuromodulation techniques capable of safely and precisely modulating the activity of deep brain structures such as the insula. ObjectiveThis study used TUS to causally investigate the respective roles of the anterior and posterior insula in urge and action control during a blink suppression task. MethodsTwenty healthy adults underwent three TUS sessions targeting the right anterior insula, posterior insula, and posterior ventricle (control site) in a within-subject, crossover design. Behavioural outcomes included blink counts and urge ratings. Additionally, voxel-based correlations were conducted to further estimate the role of each reached area with acoustic stimulation, allowing for a better mechanical understanding. ResultsTUS of the anterior insula induced a clear and acute increase in blink frequency without altering urge, reinforced by voxel-based analyses, confirming its role in voluntary action control. Posterior insula stimulation induced delayed increases in both blinks and urge, which are essentially explained by an involuntary stimulation of the right inferior frontal gyrus. Ventricular stimulation unexpectedly reduced blink frequency during the stimulation only, correlated with acoustic energy delivered within the posterior internal capsule. No significant side effects or temperature rises were observed. ConclusionsThese findings provide the first causal evidence that TUS can modulate the two main features of TS: premonitory urge and action control. Distinct effects across targets highlight the anterior insulas critical role in action control and suggest the internal capsule as a potential therapeutic target for TS.

neuroscience↗

bioRxiv2025

Neuro-behavioral impact of Tourette-related striatal disinhibition in rats

Tourette syndrome has been linked to reduced GABAergic inhibition, so called neural disinhibition, in the dorsal striatum. Dorsal-striatal neural disinhibition in animal models, caused by local microinfusion of GABA-A-receptor antagonists, produces striatal local field potential (LFP) spike-wave discharges and tic-like movements resembling motor tics. Here, we characterized further the neuro-behavioral impact of striatal disinhibition, by unilateral picrotoxin infusion into the anterior dorsal striatum, in adult male Lister hooded rats. In vivo electrophysiology under anesthesia revealed enhanced neuronal burst firing in the striatum, alongside spike-wave LFP discharges. In freely moving rats, striatal picrotoxin reliably induced tic-like movements, which mainly involved lifting of the contralateral forelimb and concomitant rotational movements of head and torso, as well as occasional rotations of the whole body around its long axis. Prepulse inhibition (PPI) of the acoustic startle response was not affected, but startle reactivity tended to be reduced. Both locomotor and non-ambulatory movements, measured in photo-beam cages, were increased. Our findings suggest that, apart from generating tic-like movements, dorsal striatal disinhibition may contribute to hyperactivity, which is often comorbid with Tourette syndrome. Enhanced striatal burst firing may be important for these behavioral effects. Our findings do not support that striatal disinhibition contributes to PPI disruption, which has been associated with Tourette syndrome and suggested to contribute to tic generation. Significance StatementStriatal disinhibition has been implicated in tic generation. Using a rat model, we show that a key neural effect of striatal disinhibition is enhanced firing of striatal neurons in bursts. We also characterized further the tic-like movements caused by unilateral disinhibition of the anterior dorsal striatum. These mainly involved lifting of the contralateral forelimb and concomitant rotational movements of head and torso, as well as occasional rotations of the whole body around its long axis. Striatal disinhibition did not affect prepulse inhibition (PPI) but caused locomotor hyperactivity. This suggests that striatal disinhibition may contribute to the general hyperactivity often comorbid with Tourette syndrome, but that other brain mechanisms underlie the PPI deficits that have been reported in the condition.

neuroscience↗

bioRxiv2024

An investigation of the effects of α and β-frequency neural entrainment using tACS on phase-aligned TMS-evoked corticospinal excitability

Deep brain stimulation [DBS] is an effective treatment for many brain disorders (e.g., Parkinsons disease), has a favourable adverse effect profile, and can be particularly effective for individuals with treatment resistant symptoms. DBS is, however, inaccessible for most individuals, is extremely expensive, and is not considered suitable for children and adolescents. For these reasons, non-invasive alternatives to DBS, such as transcranial magnetic stimulation [TMS], are increasingly being sought to treat brain health conditions. Unfortunately, current TMS approaches exhibit large intra- and inter-subject variability in their efficacy, which limits their use clinically. One likely reason for this is that TMS is invariably delivered without reference to ongoing brain activity (i.e., open loop). We propose that the efficacy of stimulation might be improved, and the variability of its effects reduced, if stimulation could be synchronised with ongoing brain activity. To investigate this, we used transcranial alternating current stimulation (tACS) to induce entrainment of brain activity at two frequencies (=10 Hz and {beta}=20 Hz), and we delivered single pulse TMS that was temporally aligned with the phase of each tACS oscillation. To investigate the effects of tACS-phase-aligned TMS we measured motor-evoked potentials (MEPs). Our findings confirm that for -tACS and {beta}-tACS both corticospinal excitability and inter-trial variability varied as a function of tACS phase. Importantly, however, the tACS phase angle that produced maximum TMS-evoked excitability was different for -tACS and {beta}-tACS; coinciding with the negative peak (trough) for -tACS and the positive peak (peak) for {beta}-tACS. These findings confirm that aligning non-invasive brain stimulation to ongoing brain activity may increase the efficacy of TMS and reduce the variability of its effects. However, our results illustrate that the optimal phase of the tACS cycle at which to deliver TMS may vary for different tACS frequencies.

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↗

bioRxiv2021

Convergent selection on juvenile hormone signaling is associated with the evolution of eusociality in bees

Sweat bees have repeatedly gained and lost eusociality, a transition from individual to group reproduction. Here, we generate chromosome-length genome assemblies for 17 species and identify genomic signatures of evolutionary trade-offs associated with transitions between social and solitary living. Both young genes and regulatory regions show enrichment for these molecular patterns. We also identify loci that show evidence of complementary signals of positive and relaxed selection linked specifically to the convergent gains and losses of eusociality in sweat bees. This includes two proteins that bind and transport juvenile hormone (JH) - a key regulator of insect development and reproduction. We find one of these JH binding proteins is primarily expressed in subperineurial glial cells that form the insect blood-brain barrier and that brain levels of JH vary by sociality. Our findings are consistent with a role of JH in modulating social behavior and suggest eusocial evolution was facilitated by alteration of the proteins that bind and transport JH, revealing how an ancestral, developmental hormone may have been co-opted during one of lifes major transitions. More broadly, our results highlight how trade-offs have structured the molecular basis of eusociality in these bees and demonstrate how both directional selection and release from constraint can shape trait evolution.

evolutionary biology↗

bioRxiv2020

The Oscillatory Effects of Rhythmic Median Nerve Stimulation

Entrainment of brain oscillations can be achieved using rhythmic non-invasive brain stimulation, and stimulation of the motor cortex at a frequency associated with sensorimotor inhibition can impair motor responses. Despite the potential for therapeutic application, these techniques do not lend themselves to use outside of a clinical setting. Here, the aim was to investigate whether rhythmic median nerve stimulation (MNS) could be used to entrain oscillations related to sensorimotor inhibition. MEG data were recorded from 20 participants during 400 trials, where for each trial 10 pulses of MNS were delivered either rhythmically or arrhythmically at 12 or 20Hz. Our results demonstrate a frequency specific increase in relative amplitude in the contralateral somatosensory cortex during rhythmic but not arrhythmic stimulation. This was coupled with an increase in inter-trial phase coherence at the same frequency, suggesting that the oscillations synchronised with the pulses of MNS. While the results show that 20Hz rhythmic peripheral nerve stimulation can produce entrainment, the response to 12Hz stimulation was largely due to the presence of rhythmic sensory evoked potentials. Regardless, rhythmic MNS resulted in synchronous firing of neuronal populations within the contralateral somatosensory cortex meaning these neurons were occupied in processing of the afferent input. Therefore, MNS could prove therapeutically useful in disorders associated with hyperexcitability within the sensorimotor cortices.

neuroscience↗

bioRxiv2020

Examining the neural antecedents of tics in Tourette syndrome using electroencephalography

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. Importantly, 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 tics are most often referred to as involuntary movements, it has been argued that tics should be viewed as voluntary movements that are executed in response to the presence of PU and bring temporary relief from the uncomfortable bodily sensations that are associated with PU. This issue remains unresolved but has very important implications for the design of clinical interventions for TS. To investigate this issue further, we conducted a study using electroencephalography (EEG). Specifically, we recorded movement-related EEG (mu and beta band oscillations) during (a) the immediate period leading up to the execution of voluntary movements by a group of individuals with TS and a group of matched healthy control participants, and (b) the immediate period leading up to the execution of a tic in a group of individuals with TS. We demonstrate that movement-related mu and beta band oscillations are not observed prior to tics in individuals with TS. We interpret this effect as reflecting the greater involvement of a network of brain areas, including the insular and cingulate cortices, basal ganglia nuclei, and the cerebellum, in the generation of tics in TS. We also show that beta-band desynchronization does occur when individuals with TS initiate voluntary movements, but, in contrast to healthy controls, desynchronization of mu-band oscillations is not observed during the execution of voluntary movements for individuals with TS. We interpret this finding as reflecting a dysfunction of physiological inhibition in TS, thereby contributing to an impaired ability to suppress neuronal populations that may compete with movement preparation processes.

neuroscience↗

bioRxiv2020

Somatomotor cortical representations are predicted by levels of short-interval intracortical inhibition

Transcranial magnetic stimulation (TMS) can be used to probe for the location of cortical somatomotor representations in humans. These somatomotor representations are dynamic and are perturbed following motor training, systematic intervention, and in disease. Evidence suggests that these representations are maintained by the inhibitory neurotransmitter gamma-Aminobutyric acid (GABA). In the current study, we quantified the location, outline, and variability of the first dorsal interosseous (FDI) hand muscle somatomotor representation using a novel rapid-acquisition TMS method in 14 healthy young volunteers. In addition, resting motor thresholds were measured using established protocols. TMS was also used to examine short-interval intracortical inhibition (SICI), which is thought to measure transiently activated cortical gamma-Aminobutyric acid (GABA) interneurons. Using stepwise regression, our results showed that the level of intracortical inhibition was a significant predictor of the FDI somatomotor representation suggesting that greater excitability of the hand area representation is possibly governed by greater activation of transient GABA interneurons.

neuroscience↗

bioRxiv2020

Entraining movement-related brain oscillations using rhythmic median nerve stimulation

Non-invasive brain stimulation techniques delivered to cortical motor areas have been shown previously to: modulate cortical motor excitability; entrain brain oscillations; and influence motor behavior; and have therefore attracted considerable interest as potential therapeutic approaches targeted for the treatment of movement disorders. However, these techniques are most often not suitable for treatment outside of the clinic, or for use with young children. We therefore investigated directly whether rhythmic pulses of median nerve stimulation (MNS) could be used to entrain brain oscillations linked to the suppression of movement. Using electroencephalography techniques together with concurrent MNS we demonstrate that 10 pulses of rhythmic MNS, delivered at 19Hz, is sufficient to entrain Beta-band brain oscillations within the contralateral sensorimotor cortex, whereas 10-pulse trains of arrhythmic MNS does not. This approach has potential in our view to be developed into a non-drug therapeutic device suitable for use outside of the research laboratory or the clinic with brain health conditions associated by excessive movements.

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↗

bioRxiv2019

Modulating brain networks with transcranial magnetic stimulation over the primary motor cortex: a concurrent TMS/fMRI study

Stimulating the primary motor cortex (M1) using transcranial magnetic stimulation (TMS) causes unique multisensory experience such as the targeted muscle activity, afferent/reafferent sensory feedback, tactile sensation over the scalp and click sound. Although the human M1 has been intensively investigated using TMS, the experience of the M1 stimulation has not been elucidated at the whole brain. Here, using concurrent TMS/fMRI, we investigated the acute effect of the M1 stimulation of functional brain networks during task and at rest. A short 1Hz train of TMS pulses applied to individuals hand area in the M1 during motor execution or at rest. Employing the independent component analysis (ICA), we showed the M1 stimulation decreased the motor networks activity when the networks were engaged in the task and increased the deactivation of networks when the networks were not involved in the ongoing task. The M1 stimulation induced the activation in the key networks involved in bodily self-consciousness (BSC) including the insular and rolandic operculum systems regardless of states. The degree of activation in these networks was highest at rest compared to during task, showing the state-dependent TMS effect. Furthermore, we demonstrated that the M1 stimulation modulated other domain general networks such as the default mode network and attention network and the inter-network connectivity between these networks. Our results showed that the M1 stimulation induced the widespread changes in the brain at the targeted system as well as non-motor, remote brain networks, specifically related to the BSC. Our findings shed light on understanding the neural mechanism of the complex and multisensory experience of the M1 stimulation.

neuroscience↗