Controversies Surrounding the Pathophysiology of Tics

2019 ◽  
Vol 34 (13) ◽  
pp. 851-862 ◽  
Author(s):  
Harvey S. Singer ◽  
Farhan Augustine
Keyword(s):  
Animal Model ◽  
Basal Ganglia ◽  
Tourette Syndrome ◽  
Model Studies ◽  
Complex Interactions ◽  
Motor Movements ◽  
Premonitory Urge ◽  
Underlying Pathophysiology

Tics are sudden, rapid, recurrent, nonrhythmic motor movements or vocalizations (phonic productions) that are commonly present in children and are required symptoms for the diagnosis of Tourette syndrome. Despite their frequency, the underlying pathophysiology of tics/Tourette syndrome remains unknown. In this review, we discuss a variety of controversies surrounding the pathophysiology of tics, including the following: Are tics voluntary or involuntary? What is the role of the premonitory urge? Are tics due to excess excitatory or deficient inhibition? Is it time to adopt the contemporary version of the cortico-basal ganglia-thalamocortical (CBGTC) circuit? and Do we know the primary abnormal neurotransmitter in Tourette syndrome? Data from convergent clinical and animal model studies support complex interactions among the various CBGTC sites and neurotransmitters. Advances are being made; however, numerous pathophysiologic questions persist.

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

2021 ◽  
Author(s):  
Stephen R. Jackson ◽  
Hilmar P. Sigurdsson ◽  
Katherine Dyke ◽  
Maria Condon ◽  
Georgina M. Jackson
Keyword(s):  
Tourette Syndrome ◽  
Cingulate Cortex ◽  
Motor Tics ◽  
Premonitory Urge

Chemoprevention of Tumors: The Role of RAR-Beta

2003 ◽  
Vol 18 (1) ◽  
pp. 78-81 ◽  
Author(s):  
S. Toma ◽  
L. Emionite ◽  
G. Fabia ◽  
N. Spadini ◽  
L. Vergani
Keyword(s):  
Animal Model ◽  
Invasive Cancer ◽  
Model Studies ◽  
Chemical Agents ◽  
Different Types ◽  
Scientific Rationale ◽  
Cellular Alterations

Chemoprevention can be defined as the use of specific natural or synthetic chemical agents to reverse, suppress, or prevent carcinogenic progression to invasive cancer. The knowledge of carcinogenic mechanisms provides the scientific rationale for chemoprevention. Epithelial carcinogenesis proceeds through multiple discernible stages of molecular and cellular alterations. Understanding of the multistep nature of carcinogenesis has evolved through highly controlled animal carcinogenesis studies, and these studies have identified three distinct phases: initiation, promotion and progression. Animal model studies have provided evidence that the development of cancer involves many different factors, including alterations in the structures and functions of different genes. Transitions between successive stages can be enhanced or inhibited in the laboratory by different types of agents, such activities providing the fundamental basis for chemoprevention.

A Reinforcement-learning Account of Tourette Syndrome

2017 ◽  
Vol 41 (S1) ◽  
pp. S10-S10
Author(s):  
T. Maia
Keyword(s):  
Reinforcement Learning ◽  
Basal Ganglia ◽  
Tourette Syndrome ◽  
Behavioral Therapy ◽  
Mathematical Explanation ◽  
Reversal Training ◽  
Computational Theory ◽  
Habit Reversal Training ◽  
Habit Learning

BackgroundTourette syndrome (TS) has long been thought to involve dopaminergic disturbances, given the effectiveness of antipsychotics in diminishing tics. Molecular-imaging studies have, by and large, confirmed that there are specific alterations in the dopaminergic system in TS. In parallel, multiple lines of evidence have implicated the motor cortico-basal ganglia-thalamo-cortical (CBGTC) loop in TS. Finally, several studies demonstrate that patients with TS exhibit exaggerated habit learning. This talk will present a computational theory of TS that ties together these multiple findings.MethodsThe computational theory builds on computational reinforcement-learning models, and more specifically on a recent model of the role of the direct and indirect basal-ganglia pathways in learning from positive and negative outcomes, respectively.ResultsA model defined by a small set of equations that characterize the role of dopamine in modulating learning and excitability in the direct and indirect pathways explains, in an integrated way: (1) the role of dopamine in the development of tics; (2) the relation between dopaminergic disturbances, involvement of the motor CBGTC loop, and excessive habit learning in TS; (3) the mechanism of action of antipsychotics in TS; and (4) the psychological and neural mechanisms of action of habit-reversal training, the main behavioral therapy for TS.ConclusionsA simple computational model, thoroughly grounded on computational theory and basic-science findings concerning dopamine and the basal ganglia, provides an integrated, rigorous mathematical explanation for a broad range of empirical findings in TS.Disclosure of interestThe author has not supplied his declaration of competing interest.

The Pathophysiology of Tics; An Evolving Story

2020 ◽  
Vol 15 (2) ◽  
pp. 92-123 ◽  
Author(s):  
Harvey S. Singer ◽  
Farhan Augustine
Keyword(s):  
Motor Control ◽  
Primary Motor Cortex ◽  
Scientific Data ◽  
Anatomical Site ◽  
Pathophysiological Mechanism ◽  
Model Studies ◽  
Complex Disorder ◽  
Complex Integration ◽  
Motor Movements

Background: Tics, defined as quick, rapid, sudden, recurrent, non-rhythmic motor movements or vocalizations are required components of Tourette Syndrome (TS) - a complex disorder characterized by the presence of fluctuating, chronic motor and vocal tics, and the presence of co-existing neuropsychological problems. Despite many advances, the underlying pathophysiology of tics/TS remains unknown. Objective: To address a variety of controversies surrounding the pathophysiology of TS. More specifically: 1) the configuration of circuits likely involved; 2) the role of inhibitory influences on motor control; 3) the classification of tics as either goal-directed or habitual behaviors; 4) the potential anatomical site of origin, e.g. cortex, striatum, thalamus, cerebellum, or other(s); and 5) the role of specific neurotransmitters (dopamine, glutamate, GABA, and others) as possible mechanisms (Abstract figure). Methods: Existing evidence from current clinical, basic science, and animal model studies are reviewed to provide: 1) an expanded understanding of individual components and the complex integration of the Cortico-Basal Ganglia-Thalamo-Cortical (CBGTC) circuit - the pathway involved with motor control; and 2) scientific data directly addressing each of the aforementioned controversies regarding pathways, inhibition, classification, anatomy, and neurotransmitters. Conclusion: Until a definitive pathophysiological mechanism is identified, one functional approach is to consider that a disruption anywhere within CBGTC circuitry, or a brain region inputting to the motor circuit, can lead to an aberrant message arriving at the primary motor cortex and enabling a tic. Pharmacologic modulation may be therapeutically beneficial, even though it might not be directed toward the primary abnormality.

scholarly journals The Role of Osteopontin in Amyotrophic Lateral Sclerosis: A Systematic Review

2020 ◽  
Vol 7 (3) ◽  
Author(s):  
Seyed Vahid Mousavi ◽  
Elmira Agah ◽  
Abbas Tafakhori
Keyword(s):  
Animal Model ◽  
Amyotrophic Lateral Sclerosis ◽  
Cortical Neurons ◽  
Human Studies ◽  
Cochrane Library ◽  
Control Group ◽  
Model Studies ◽  
Als Patients ◽  
Lateral Sclerosis

Context: Osteopontin (OPN) is a matrix phosphoprotein expressed by a variety of tissues and cells, including the immune system and the nervous system. Previous studies have shown that OPN may have a role in neurodegenerative diseases, including multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. Objectives: The present study aimed to systematically review studies investigating the role of OPN in amyotrophic lateral sclerosis (ALS) patients or the disease animal model. Evidence Acquisition: We searched the Cochrane Library, PubMed, Web of Science, and Scopus to find relevant articles published up to January 20, 2019. Both human and animal model studies of ALS were considered. Results: A total of nine articles (four human studies and five animal model studies) were included. Two of the human studies reported that the CSF levels of OPN were higher among ALS patients compared to controls. The other two human studies found that OPN levels in cortical neurons did not differ significantly between ALS cases and the non-neurological control group. One of the studies found that the expression level of OPN in astrocytes was similar between ALS patients and the control group, but the level of microglial OPN significantly increased in ALS cases. Four of the animal model studies reported that the expression of OPN mRNA in spinal cord microglia significantly increased during the disease progression. The remaining animal model study found that OPN was selectively expressed by fast fatigue-resistant and slow motor neurons (MNs), which are resistant to ALS, and that the OPN expression was low among fast-fatigable MNs. Conclusions: Prompt microglial activation is a hallmark pathology of ALS, and OPN is among the most widely expressed proteins by these activated glial cells. Therefore, OPN might have a role in ALS pathogenesis. The existing evidence is not sufficient to justify whether OPN has a neurotoxic or neuroprotective role in ALS. We encourage researchers to investigate the role of OPN in ALS pathogenesis more extensively.

scholarly journals Regulating Retinoic Acid Availability during Development and Regeneration: The Role of the CYP26 Enzymes

2020 ◽  
Vol 8 (1) ◽  
pp. 6
Author(s):  
Catherine Roberts
Keyword(s):  
Animal Model ◽  
Cytochrome P450 ◽  
Retinoic Acid ◽  
Receptor Binding ◽  
Genetic Disease ◽  
Signalling Pathway ◽  
Human Genetic Disease ◽  
Model Studies ◽  
And Function

This review focuses on the role of the Cytochrome p450 subfamily 26 (CYP26) retinoic acid (RA) degrading enzymes during development and regeneration. Cyp26 enzymes, along with retinoic acid synthesising enzymes, are absolutely required for RA homeostasis in these processes by regulating availability of RA for receptor binding and signalling. Cyp26 enzymes are necessary to generate RA gradients and to protect specific tissues from RA signalling. Disruption of RA homeostasis leads to a wide variety of embryonic defects affecting many tissues. Here, the function of CYP26 enzymes is discussed in the context of the RA signalling pathway, enzymatic structure and biochemistry, human genetic disease, and function in development and regeneration as elucidated from animal model studies.

Neuropathology in Tourette Syndrome

CNS Spectrums ◽  
1999 ◽  
Vol 4 (3) ◽  
pp. 65-74 ◽  
Author(s):  
Neal R. Swerdlow ◽  
Anne B. Young
Keyword(s):  
Basal Ganglia ◽  
Tourette Syndrome ◽  
Small Samples ◽  
Dopamine Antagonists ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Hyperactivity Disorder ◽  
Efferent Projections ◽  
Made In

ABSTRACTThe unique clinical presentation of Tourette syndrome (TS) and its symptomatic response to dopamine antagonists are widely cited as evidence for the central role of the limbic-motor interface in the pathophysiology of TS. Nonetheless, the true neuropathology of TS remains elusive, even though significant advances have been made in understanding complex interconnected circuitries within the limbic system and basal ganglia. Neuropathologic and neuroimaging studies—plagued by small samples, clinical heterogeneity, and a number of interpretative problems—are generally supportive of pathology within the orbitofrontal cortex, striatum, and their efferent projections in TS. The specific patterns of abnormalities vary widely across these studies, clouding attempts to define a unifying neuropathology for this disorder. Converging yet circumstantial evidence for frontal cortical, and basal ganglia pathology in TS comes also from studies infields ranging from neuroimmunology to neuropsychology, and from the clinical overlap between TS and disorders such as obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and Sydenhams chorea. As a “model” neuropsychiatric disorder, TS has stimulated advances in several areas of neurobiology research, yet we still await a real understanding of its pathophysiology in order to move from empirically driven therapeutics to the development of targeted effective treatments.

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