Differentiating tic electrophysiology from voluntary movement in the human thalamocortical circuit

ObjectivesTourette syndrome is a neurodevelopmental disorder commonly associated with involuntary movements, or tics. We currently lack an ideal animal model for Tourette syndrome. In humans, clinical manifestation of tics cannot be captured via functional imaging due to motion artefacts and limited temporal resolution, and electrophysiological studies have been limited to the intraoperative environment. The goal of this study was to identify electrophysiological signals in the centromedian (CM) thalamic nucleus and primary motor (M1) cortex that differentiate tics from voluntary movements.MethodsThe data were collected as part of a larger National Institutes of Health-sponsored clinical trial. Four participants (two males, two females) underwent monthly clinical visits for collection of physiology for a total of 6 months. Participants were implanted with bilateral CM thalamic macroelectrodes and M1 subdural electrodes that were connected to two neurostimulators, both with sensing capabilities. MRI scans were performed preoperatively and CT scans postoperatively for localisation of electrodes. Electrophysiological recordings were collected at each visit from both the cortical and subcortical implants.ResultsRecordings collected from the CM thalamic nucleus revealed a low-frequency power (3–10 Hz) increase that was time-locked to the onset of involuntary tics but was not present during voluntary movements. Cortical recordings revealed beta power decrease in M1 that was present during tics and voluntary movements.ConclusionWe conclude that a human physiological signal was detected from the CM thalamus that differentiated tic from voluntary movement, and this physiological feature could potentially guide the development of neuromodulation therapies for Tourette syndrome that could use a closed-loop-based approach.

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Elevated Expression of SLC6A4 Encoding the Serotonin Transporter (SERT) in Gilles de la Tourette Syndrome

Genes ◽

10.3390/genes12010086 ◽

2021 ◽

Vol 12 (1) ◽

pp. 86

Author(s):

Mathis Hildonen ◽

Amanda M. Levy ◽

Christina Dahl ◽

Victoria A. Bjerregaard ◽

Lisbeth Birk Møller ◽

...

Keyword(s):

Tourette Syndrome ◽

Serotonin Transporter ◽

Neurodevelopmental Disorder ◽

Control Group ◽

Obsessive Compulsive ◽

Expression Levels ◽

Compulsive Disorder ◽

Hyperactivity Disorder ◽

Elevated Expression ◽

Gene Expression Levels

Gilles de la Tourette syndrome (GTS) is a complex neurodevelopmental disorder characterized by motor and vocal tics. Most of the GTS individuals have comorbid diagnoses, of which obsessive-compulsive disorder (OCD) and attention deficit-hyperactivity disorder (ADHD) are the most common. Several neurotransmitter systems have been implicated in disease pathogenesis, and amongst these, the dopaminergic and the serotonergic pathways are the most widely studied. In this study, we aimed to investigate whether the serotonin transporter (SERT) gene (SLC6A4) was differentially expressed among GTS individuals compared to healthy controls, and whether DNA variants (the SERT-linked polymorphic region 5-HTTLPR, together with the associated rs25531 and rs25532 variants, and the rare Ile425Val variant) or promoter methylation of SLC6A4 were associated with gene expression levels or with the presence of OCD as comorbidity. We observed that SLC6A4 expression is upregulated in GTS individuals compared to controls. Although no specific genotype, allele or haplotype was overrepresented in GTS individuals compared to controls, we observed that the LAC/LAC genotype of the 5-HTTLPR/rs25531/rs25532 three-locus haplotype was associated with higher SLC6A4 mRNA expression levels in GTS individuals, but not in the control group.

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In search for the most optimal EEG method: A practical evaluation of a water-based electrode EEG system

Brain and Neuroscience Advances ◽

10.1177/23982128211053698 ◽

2021 ◽

Vol 5 ◽

pp. 239821282110536

Author(s):

Marta Topor ◽

Bertram Opitz ◽

Philip J. A. Dean

Keyword(s):

Signal To Noise Ratio ◽

Flanker Task ◽

Low Frequency ◽

Noise Levels ◽

Slow Drift ◽

Practical Evaluation ◽

Beta Power ◽

Water Based ◽

High Beta ◽

Frequency Power

The study assessed a mobile electroencephalography system with water-based electrodes for its applicability in cognitive and behavioural neuroscience. It was compared to a standard gel-based wired system. Electroencephalography was recorded on two occasions (first with gel-based, then water-based system) as participants completed the flanker task. Technical and practical considerations for the application of the water-based system are reported based on participant and experimenter experiences. Empirical comparisons focused on electroencephalography data noise levels, frequency power across four bands (theta, alpha, low beta and high beta) and event-related components (P300 and ERN). The water-based system registered more noise compared to the gel-based system which resulted in increased loss of data during artefact rejection. Signal-to-noise ratio was significantly lower for the water-based system in the parietal channels which affected the observed parietal beta power. It also led to a shift in topography of the maximal P300 activity from parietal to frontal regions. The water-based system may be prone to slow drift noise which may affect the reliability and consistency of low-frequency band analyses. Practical considerations for the use of water-based electrode electroencephalography systems are provided.

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Temporal discounting in adolescents and adults with Tourette syndrome

PLoS ONE ◽

10.1371/journal.pone.0253620 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0253620

Author(s):

Canan Beate Schüller ◽

Ben Jonathan Wagner ◽

Thomas Schüller ◽

Juan Carlos Baldermann ◽

Daniel Huys ◽

...

Keyword(s):

Tourette Syndrome ◽

Positive Reinforcement ◽

Intertemporal Choice ◽

Neurodevelopmental Disorder ◽

Temporal Discounting ◽

Hyperbolic Discounting ◽

Developmental Trajectory ◽

Adult Patients ◽

Control Functions ◽

Male Subjects

Tourette syndrome is a neurodevelopmental disorder associated with hyperactivity in dopaminergic networks. Dopaminergic hyperactivity in the basal ganglia has previously been linked to increased sensitivity to positive reinforcement and increases in choice impulsivity. In this study, we examine whether this extends to changes in temporal discounting, where impulsivity is operationalized as an increased preference for smaller-but-sooner over larger-but-later rewards. We assessed intertemporal choice in two studies including nineteen adolescents (age: mean[sd] = 14.21[±2.37], 13 male subjects) and twenty-five adult patients (age: mean[sd] = 29.88 [±9.03]; 19 male subjects) with Tourette syndrome and healthy age- and education matched controls. Computational modeling using exponential and hyperbolic discounting models via hierarchical Bayesian parameter estimation revealed reduced temporal discounting in adolescent patients, and no evidence for differences in adult patients. Results are discussed with respect to neural models of temporal discounting, dopaminergic alterations in Tourette syndrome and the developmental trajectory of temporal discounting. Specifically, adolescents might show attenuated discounting due to improved inhibitory functions that also affect choice impulsivity and/or the developmental trajectory of executive control functions. Future studies would benefit from a longitudinal approach to further elucidate the developmental trajectory of these effects.

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A New Capacitance Multiplier Structure with High Multiplication Factor for Ultra-Low-Frequency Filter in Biomedical Applications

Journal of Circuits System and Computers ◽

10.1142/s0218126620501091 ◽

2019 ◽

Vol 29 (07) ◽

pp. 2050109

Author(s):

Yan Li ◽

Yong Liang Li

Keyword(s):

Biomedical Applications ◽

Low Frequency ◽

Multiplication Factor ◽

Frequency Filter ◽

Pass Filter ◽

Low Pass Filter ◽

Physiological Signal ◽

Wide Range ◽

Low Pass ◽

Capacitance Multiplier

A novel capacitance multiplier is proposed to implement an ultra-low-frequency filter for physiological signal processing in biomedical applications. With the proposed multiplier, a simple first-order low-pass filter achieves a [Formula: see text]3-dB frequency of 33.4[Formula: see text]μHz with a 1-pF capacitance and a 20[Formula: see text]k[Formula: see text] resistance. This corresponds to a multiplication factor of as large as [Formula: see text]. By changing the controlling terminal, the [Formula: see text]3-dB frequency can be tuned in a wide range of 33.4[Formula: see text]μHz–6.3[Formula: see text]kHz.

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Early infantile epileptic-dyskinetic encephalopathy due to biallelic PIGP mutations

Neurology Genetics ◽

10.1212/nxg.0000000000000387 ◽

2020 ◽

Vol 6 (1) ◽

pp. e387 ◽

Cited By ~ 7

Author(s):

Annalisa Vetro ◽

Tiziana Pisano ◽

Silvia Chiaro ◽

Elena Procopio ◽

Azzurra Guerra ◽

...

Keyword(s):

Neurodevelopmental Disorder ◽

Brain Mri ◽

Molecular Genetic ◽

Genetic Diagnosis ◽

Premature Death ◽

Epileptic Encephalopathy ◽

Whole Exome ◽

Mri Scans ◽

Severe Hypotonia ◽

Profound Disability

ObjectiveTo describe clinical, biochemical, and molecular genetic findings in a large inbred family in which 4 children with a severe early-onset epileptic-dyskinetic encephalopathy, with suppression burst EEG, harbored homozygous mutations of phosphatidylinositol glycan anchor biosynthesis, class P (PIGP), a member of the large glycosylphosphatidylinositol (GPI) anchor biosynthesis gene family.MethodsWe studied clinical features, EEG, brain MRI scans, whole-exome sequencing (WES), and measured the expression of a subset of GPI-anchored proteins (GPI-APs) in circulating granulocytes using flow cytometry.ResultsThe 4 affected children exhibited a severe neurodevelopmental disorder featuring severe hypotonia with early dyskinesia progressing to quadriplegia, associated with infantile spasms, focal, tonic, and tonic-clonic seizures and a burst suppression EEG pattern. Two of the children died prematurely between age 2 and 12 years; the remaining 2 children are aged 2 years 7 months and 7 years 4 months. The homozygous c.384del variant of PIGP, present in the 4 patients, introduces a frame shift 6 codons before the expected stop signal and is predicted to result in the synthesis of a protein longer than the wild type, with impaired functionality. We demonstrated a reduced expression of the GPI-AP CD16 in the granulocytic membrane in affected individuals.ConclusionsPIGP mutations are consistently associated with an epileptic-dyskinetic encephalopathy with the features of early infantile epileptic encephalopathy with profound disability and premature death. CD16 is a valuable marker to support a genetic diagnosis of inherited GPI deficiencies.

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