Biology subjects

Black, K. J.

Publications and source records attributed to Black, K. J..

7 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↗

bioRxiv2020

Hippocampal volume in Provisional Tic Disorder predicts tic severity at 12-month follow-up

BackgroundPrevious studies have investigated differences in the volumes of subcortical structures (e.g., caudate nucleus, putamen, thalamus, amygdala, hippocampus) between individuals with and without Tourette syndrome (TS), as well as the relationships between these volumes and tic symptom severity. These volumes may also predict clinical outcome in Provisional Tic Disorder (PTD), but that hypothesis has never been tested. ObjectiveThis study aimed to examine whether the volumes of subcortical structures measured shortly after tic onset can predict tic symptom severity at one year post tic onset, when TS can first be diagnosed. MethodsWe obtained T1-weighted structural MRI scans from 41 children with PTD (25 with prospective motion correction [vNavs]) whose tics had begun less than 9 months (median 3.7 months) prior to the first study visit (baseline). We re-examined them at the 12-month anniversary of their first tic (follow-up), assessing tic severity using the Yale Global Tic Severity Scale. We quantified the volumes of subcortical structures using volBrain software. ResultsBaseline hippocampal volume was correlated with tic severity at the 12-month follow-up, with a larger hippocampus at baseline predicting worse tic severity at follow-up. This result was confirmed in the subgroup scanned with prospective motion correction. The volumes of other subcortical structures did not significantly predict tic severity at follow-up. ConclusionThese findings suggest that hippocampal volume may be an important marker in predicting prognosis in Provisional Tic Disorder.

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bioRxiv2019

Dopamine buffering capacity imaging: A pharmacodynamic fMRI method for staging Parkinson disease

We propose a novel brain imaging method for objectively quantifying disease severity in Parkinson disease (PD). Levodopa pharmacological fMRI (phMRI) hysteresis mapping is based on the clinical observation that the benefit from a dose of levodopa wears off more quickly as PD progresses. Biologically this has been thought to represent decreased buffering capacity for dopamine as nigrostriatal cells die. Buffering capacity has been modeled previously based on clinical effects, but clinical measurements are influenced by confounding factors such as patient fatigue. The new method proposes to measure the effect directly and objectively based on the timing of the known metabolic and blood flow response of several brain regions to exogenous levodopa. Such responses are robust and can be quantified without ionizing radiation using perfusion MRI.\n\nHere we present simulation studies based on published clinical dose-response data and an intravenous levodopa infusion. Standard pharmacokinetic-pharmacodynamic methods were used to model the response. Then the effect site rate constant ke was estimated from simulated response data plus Gaussian noise.\n\nPredicted time:effect curves sampled at times consistent with phMRI differ substantially based on clinical severity. Estimated ke from noisy input data was recovered with good accuracy.\n\nThese simulation results support the feasibility of levodopa phMRI hysteresis mapping to measure the severity of dopamine denervation objectively and simultaneously in several brain regions.

neuroscience↗

bioRxiv2018

The urge to blink in Tourette syndrome

Functional neuroimaging studies have attempted to explore brain activity that occurs with tic occurrence in subjects with Tourette syndrome (TS). However, they are limited by the difficulty of disambiguating brain activity required to perform a tic, or activity caused by the tic, from brain activity that generates a tic. Inhibiting the urge to tic is important to patients experience of tics and we hypothesize that inhibition of a compelling motor response to a natural urge will differ in TS subjects compared to controls. This study examines the urge to blink, which shares many similarities to premonitory urges to tic. Previous neuroimaging studies with the same hypothesis have used a one-size-fits-all approach to extract brain signal putatively linked to the urge to blink. We aimed to create a subject-specific and blink-timing-specific pathophysiological model, derived from out-of-scanner blink suppression trials, to eventually better interpret blink suppression fMRI data. Eye closure and continuously self-reported discomfort were reported during five blink suppression trials in 30 adult volunteers, 15 with a chronic tic disorder. For each subject, data from four of the trials were used with an empirical mathematical model to predict discomfort from eye closure observed during the remaining trial. The blink timing model of discomfort during blink suppression predicted observed discomfort much better than previously applied models. However, so did a model that simply reflected the mean time-discomfort curves from each subjects other trials. The TS group blinked more than twice as often during the blink suppression block, and reported higher baseline discomfort, smaller excursion from baseline to peak discomfort during the blink suppression block, and slower return of discomfort to baseline during the recovery block. Combining this approach with observed eye closure during fMRI blink suppression trials should therefore extract brain signal more tightly linked to the urge to blink.

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bioRxiv2018

Atypical functional connectivity in Tourette syndrome differs between children and adults

BackgroundTourette syndrome (TS) is a neuropsychiatric disorder characterized by motor and vocal tics that typically change over development. Whether and how brain function in TS also differs across development has been largely understudied. Here, we used functional connectivity MRI to examine whole brain functional networks in children and adults with TS.\n\nMethodsMultivariate classification methods were used to find patterns among functional connections that distinguish TS from controls separately for children and adults (total N = 202). We tested whether the patterns of connections that classify diagnosis in one age group (e.g., children) could classify diagnosis in another age group (e.g., adults). We also tested whether the developmental trajectory of these connections were altered in TS.\n\nResultsPatterns of functional connections that distinguished TS from controls were generalizable to an age-matched independent test set, but not to other age groups. While diagnostic classification was successful in children and adults separately, the connections that best distinguished TS from controls were age-specific. When contextualized with typical development, some functional connections exhibited accelerated maturation in childhood TS, while others exhibited delayed maturation in adulthood TS.\n\nConclusionsOur results demonstrate that brain networks are differentially altered in children and adults with TS, and that the developmental trajectory of affected connections is disrupted. These findings further our understanding of neurodevelopmental trajectories in TS and carry implications for future applications aimed at predicting the clinical course of TS in individuals over development.

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bioRxiv2017

Patterns and predictors of tic suppressibility in youth with tic disorders

Background: Tic suppression is the primary target of tic disorder treatment, but factors that influence voluntary tic inhibition are not well understood. Several studies using the Tic Suppression Task have demonstrated significant inter-individual variability in tic suppressibility but have individually been underpowered to address correlates of tic suppression. The present study explored patterns and clinical correlates of tic suppression in youth with tic disorders using a large, pooled dataset.\n\nMethods: Individual-level data from 9 studies using the Tic Suppression Task were pooled, yielding a sample of 99 youth with tic disorders. Analyses examined patterns of tic suppressibility and the relationship between tic suppressibility and demographic and clinical characteristics.\n\nResults: A large majority of youth demonstrated a high degree of tic suppression, but heterogeneous patterns of tic suppressibility were also observed. Better tic suppressibility was related to older age and more frequent tics but unrelated to other clinical variables, including presence of psychiatric comorbidity, psychotropic medication status, and tic and premonitory urge severity.\n\nConclusions: The mechanisms underlying the observed heterogeneity in tic suppressibility warrant further investigation. The Tic Suppression Task is a promising method for testing mechanistic hypotheses related to tic suppression.

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bioRxiv2017

Mapping Movement, Mood, Motivation, and Mentation in the Subthalamic Nucleus

The anatomical connections of the subthalamic nucleus (STN) have driven hypotheses about its functional anatomy, including the hypothesis that the precise anatomical location of STN deep brain stimulation (DBS) determines the variability of motor and non-motor responses across Parkinson disease (PD) patients. We previously tested that hypothesis using a three-dimensional (3D) statistical method to interpret the acute effects of unilateral DBS at each patients clinically optimized DBS settings and active contact. Here we report a similar analysis from a new study in which DBS parameters were standardized and DBS locations were chosen blind to clinical response. In 74 individuals with PD and STN DBS, STN contacts were selected near the dorsal and ventral border of the STN contralateral to the more affected side of the body. Participants were tested off PD medications in each of 3 conditions (ventral STN DBS, dorsal STN DBS and DBS off) for acute effects on mood, apathy, working memory, response inhibition and motor function. Voltage, frequency, and pulse width were standardized, and participants and raters were blind to condition. In a categorical analysis, both dorsal and ventral STN DBS improved mean motor function without affecting cognitive measures. Dorsal STN DBS induced greater improvement in rigidity than ventral STN DBS, whereas ventral STN DBS was more effective for improving anxiety and mood. In the 3D analysis, contact location was significant only for bradykinesia and resting tremor, with the greatest improvement occurring with DBS in dorsal STN and zona incerta. These results provide new, direct functional evidence for the anatomically-derived model of STN using the novel 3D analysis, in which motor function is most represented in dorsal STN. However, our data suggest that functional segregation between motor and non-motor areas of the STN is limited, since locations that induced improvements in motor function and mood overlapped substantially.

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