Materiały źródłowe

• #1 Pathophysiology of tic disorders – PubMed

  https://pubmed.ncbi.nlm.nih.gov/26179434/

  Tics are the defining symptom of Tourette syndrome and other tic disorders (TDs); however, they form only a part of their overall symptoms. The recent surge of studies addressing the underlying pathophysiology of tics has revealed an intricate picture involving multiple brain areas and complex pathways. […] Distinct brain pathways mediate the expression of tics, whereas others are involved in the generation of the premonitory urge, associated comorbidities, and other changes in brain state. Expression of these symptoms is controlled by additional networks underlying voluntary suppression by the patient or those reflecting overall behavioral state. […] Thus, involvement of the corticobasal ganglia pathway and its interaction with motor, sensory, limbic, and executive networks in each of the components as well as their control by different neuromodulators is described. This division enables a focused definition of the neuronal systems involved in each of these processes and allows a better understanding of the pathophysiology of TDs as a whole.

• #2 Merging the Pathophysiology and Pharmacotherapy of Tics

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6329776/

  Anatomically, cortical-basal ganglia-thalamo-cortical (CBGTC) circuits have an essential role in the expression of tics. […] The precise primary site of abnormality for tics remains undetermined. Although many pathophysiologic hypotheses favor a specific abnormality of the cortex, striatum, or globus pallidus, others recognize essential influences from regions such as the thalamus, cerebellum, brainstem, and ventral striatum. […] A greater understanding of the primary neurochemical defect in TS would be extremely valuable for the development of new tic-suppressing therapies. […] The goal of this review is to integrate our current understanding of the pathophysiology of TS with present and proposed pharmacotherapies for tic suppression. […] At the biochemical level, proper conveyance of messages through CBGTC circuits and the maintenance of stable connections require functionally integrated neurotransmitter systems.

• #3 Tourette syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Tourette_syndrome

  Cortico-striato-thalamo-cortical (CSTC) circuits, or neural pathways, provide inputs to the basal ganglia from the cortex. These circuits connect the basal ganglia with other areas of the brain to transfer information that regulates planning and control of movements, behavior, decision-making, and learning. Behavior is regulated by cross-connections that „allow the integration of information” from these circuits. Involuntary movements may result from impairments in these CSTC circuits, including the sensorimotor, limbic, language and decision making pathways. Abnormalities in these circuits may be responsible for tics and premonitory urges. […] The release of dopamine in the basal ganglia is higher in people with Tourette’s, implicating biochemical changes from „overactive and dysregulated dopaminergic transmissions”.

• #4 The Pathophysiology of Tics; An Evolving Story

  https://www.eurekaselect.com/176897/article

  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. […] 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. […] The role of specific neurotransmitters (dopamine, glutamate, GABA, and others) as possible mechanisms. […] 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.

• #5 Tourette syndrome: Pathogenesis, clinical features, and diagnosis – UpToDate

  https://www.uptodate.com/contents/tourette-syndrome-pathogenesis-clinical-features-and-diagnosis

  Tourette syndrome (TS) is thought to result from a complex interaction between social and environmental factors and multiple genetic risk factors. […] TS likely results from a disturbance in the cortico-striatal-thalamic-cortical (mesolimbic) circuit, which leads to disinhibition of the motor and limbic system. […] Advanced neuroimaging studies have found evidence of structural, functional, and metabolic changes in the brain associated with TS. […] Reductions in caudate volume are the most commonly reported structural changes. […] Based on functional magnetic resonance imaging (MRI) studies, the insula plays a key role in premonitory sensations and urges, often preceding motor or phonic tics.

• #6 Tourette syndrome: Pathogenesis, clinical features, and diagnosis – UpToDate

  https://www.uptodate.com/contents/tourette-syndrome-pathogenesis-clinical-features-and-diagnosis/print

  Tourette syndrome (TS) is thought to result from a complex interaction between social and environmental factors and multiple genetic risk factors. […] TS likely results from a disturbance in the cortico-striatal-thalamic-cortical (mesolimbic) circuit, which leads to disinhibition of the motor and limbic system. […] Advanced neuroimaging studies have found evidence of structural, functional, and metabolic changes in the brain associated with TS. […] Reductions in caudate volume are the most commonly reported structural changes. […] Positron emission tomography (PET) studies have shown variable rates of glucose utilization in the basal ganglia in patients with TS compared with controls. […] Based on functional magnetic resonance imaging (MRI) studies, the insula plays a key role in premonitory sensations and urges, often preceding motor or phonic tics.

• #7 Tourette Syndrome and Other Tic Disorders: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1182258-overview

  The pathophysiology underlying TS remains unknown. Biochemical, imaging, neurophysiologic and genetic studies support the hypothesis that TS is an inherited, developmental disorder of neurotransmission. […] The basal ganglia and inferior frontal cortex have been implicated in the pathogenesis of TS, as well as obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). Neuropathological studies, however, have failed to reveal any consistent structural abnormalities in these areas. […] Volumetric MRI studies have suggested that the normal asymmetry of the basal ganglia is lost in affected individuals. Healthy right-handed males normally demonstrate a predominance of the left putamen but this appears to be absent in TS, supporting the possibility of a developmental abnormality.

• #8 Merging the Pathophysiology and Pharmacotherapy of Tics

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6329776/

  Evidence supporting a dopaminergic abnormality in TS is extensive and includes the recognition that the most effective tic-suppressing medications are dopamine receptor antagonists. […] Despite a strong sense that dopamine is involved in tic pathophysiology, due in part to inconsistent studies, hypothesized abnormalities have ranged from an increased number of postsynaptic dopamine receptors or a greater dopamine receptor affinity; increased dopamine innervation; a presynaptic dopamine abnormality; and an increased release of dopamine. […] The identification of the definitive primary neurochemical abnormality remains a challenge. […] Although controversial, the authors favor a functional involvement of the dopaminergic system, likely an alteration of phasic release.

• #9 Recognition and Management of Tourette’s Syndrome and Tic Disorders | AAFP

  https://www.aafp.org/pubs/afp/issues/1999/0415/p2263.html

  Tics are believed to result from a tripartite dysfunction in the central nervous system. […] Imaging techniques have implicated the basal ganglia and frontal cortex in the pathogenesis of Tourette’s syndrome. […] Strong evidence indicates that dopamine excess or supersensitivity of the postsynaptic dopamine receptors is the underlying pathophysiologic mechanism of Tourette’s syndrome. […] The third hypothesis of dysfunction is a neurophysiologic deficit secondary to neurotransmitter abnormalities, resulting in failure of inhibition of the frontal-subcortical motor circuits. […] As a result, the tic-related neural circuits for throat clearing, sniffing, eye squinting or facial grimacing may run too frequently and out of synchrony with those for other motor movements.

• #10 Tourette Syndrome and Other Tic Disorders: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1182258-overview

  Several studies using single-photon emission computed tomography (SPECT) have found an increase in the density of the presynaptic dopamine transporter and the postsynaptic D2 dopamine receptor. […] Some neuropathological studies have supported these findings. TS may therefore result from abnormal regulation of dopamine uptake and release. […] Substantial evidence indicates that neuroleptic and atypical antipsychotic agents reduce tic severity. Presynaptic dopamine-depleting agents also improve tics, and in some patients, tics may be worsened by neuroleptic withdrawal or, possibly, stimulant use. However, other data do not support a simple hypothesis that dopamine function is hyperactive in individuals with TS. […] In summary, clinical evidence suggests that dopaminergic function is abnormal in TS. However, the site of dopamine involvement within the pathway remains unknown.

• #11

  https://journals.lww.com/co-neurology/fulltext/2016/08000/tics_and_tourette_s__update_on_pathophysiology_and.17.aspx

  To describe recent advances in the pathophysiology of tics and Tourette syndrome, and novel insights on tic control. […] The cortico-basal ganglia-thalamo-cortical loops are implicated in generation of tics. Disruption of GABAergic inhibition lies at the core of tic pathophysiology, but novel animal models also implicate cholinergic and histaminergic neurotransmission. […] The study of Tourette syndrome pathophysiology involves different neural disciplines and provides novel, exciting insights of brain function in health and disease. These in turn provide the basis for innovative treatment approaches of tics and their associations.

• #12 Merging the Pathophysiology and Pharmacotherapy of Tics | Tremor and Other Hyperkinetic Movements

  https://tremorjournal.org/articles/10.5334/tohm.442

  Anatomically, cortical-basal ganglia-thalamo-cortical (CBGTC) circuits have an essential role in the expression of tics. […] In addition, the results of standard and emerging tic-suppressing therapies affecting nine separate neurotransmitter systems are discussed. […] The precise primary site of abnormality for tics remains undetermined. […] Although many pathophysiologic hypotheses favor a specific abnormality of the cortex, striatum, or globus pallidus, others recognize essential influences from regions such as the thalamus, cerebellum, brainstem, and ventral striatum. […] Although research and clinical evidence supports involvement of the dopaminergic system, additional data emphasizes the potential roles for several other neurotransmitter systems. […] A greater understanding of the primary neurochemical defect in TS would be extremely valuable for the development of new tic-suppressing therapies. […] Nevertheless, recognizing the varied and complex interactions that exist in a multi-neurotransmitter system, successful therapy may not require direct targeting of the primary abnormality.

• #13 Interaction of the Dopaminergic and GABAergic Systems in the Formation of Tics – Tourette Association of America

  https://tourette.org/grant/interaction-of-the-dopaminergic-and-gabaergic-systems-in-the-formation-of-tics/

  Dopaminergic dysfunction has been a primary suspect in Tourette syndromes pathophysiology; however, dopaminergic modulation does not lead, by itself, to the formation of motor tics in animal models. […] Motor tics may be induced experimentally following GABAA antagonists (such as bicuculline) microinjection in the motor domain of the striatum of both rodents and primates. […] The underlying hypothesis of the project is that dopamine modulates the primary mechanism of tic formation which is generated by abnormal local GABAergic disinhibition within the striatum. […] The interaction of these key neurotransmitter and neuromodulator systems of the striatum may serve a crucial role in understanding the mechanism underlying the formation and expression of tics in Tourette syndrome.

• #14 Tourette Syndrome and Other Tic Disorders: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1182258-overview

  Knowledge about primate basal ganglia anatomy and physiology has been summarized. In this view, motor patterns are generated in the cerebral cortex and brain stem. Performance of a specific intended movement includes not only selection of the desired movement but also inhibition of antagonistic movements and of similar movements of neighboring body parts. […] The basal ganglia are organized so as to inhibit, or apply a „brake” to these undesired motor programs. Normally, the basal ganglia allow selective release of the brake from the desired action. Tics may result from a defect in this braking function. This may be caused by an episode of overactivity in a focal subset of striatal neurons, perhaps in the striatal matrisomes identified by Graybiel and colleagues. […] The episodic focal overactivity may result from any of various mechanisms acting at any of various locations from cortex to thalamus.

• #15 Neurobiology of Tourette Syndrome: Current Status and Need for Further Investigation | Journal of Neuroscience

  https://www.jneurosci.org/content/31/35/12387

  Another proposed theory is that tics can be an acquired consequence of autoimmune mechanisms following a Group A -hemolytic streptococcal infection (GABHS) […] A series of parallel cortico-striatal-thalamo-cortical (CSTC) circuits that link specific regions of the frontal cortex to subcortical structures has provided a framework for understanding the interconnected neurobiological relationships that exist between TS and its multiple comorbid problems. […] According to this model, hyperkinetic disorders were the result of increased cortical excitability, due to either a reduction of direct pathway excitatory effect or an increase in the indirect inhibitory effect. […] Within this system, tics are viewed as a focal excitatory abnormality in the striatum that causes an erroneous inhibition of a group of neurons in the GPi and in turn a disinhibition of cortical neurons.

• #16 Dysfunctions of the basal ganglia-cerebellar-thalamo-cortical system produce motor tics in Tourette syndrome | PLOS Computational Biology

  https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005395

  Motor tics are a cardinal feature of Tourette syndrome and are traditionally associated with an excess of striatal dopamine in the basal ganglia. […] Recent evidence increasingly supports a more articulated view where cerebellum and cortex, working closely in concert with basal ganglia, are also involved in tic production. […] In particular, the model predicts that the interplay between dopaminergic signal and cortical activity contributes to triggering the tic event and that the recently discovered basal ganglia-cerebellar anatomical pathway may support the involvement of the cerebellum in tic production. […] An alteration in striatal dopamine release as in TS may induce the production of tics as a consequence of a focal excitatory abnormality in the striatum that causes an undesired disinhibition of thalamo-cortical circuits.

• #17 The Pathophysiology of Tics; An Evolving Story | CoLab

  https://colab.ws/articles/10.2174%2F1574885514666191121143930

  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. […] 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.

• #18 Nail tic disorders: Manifestations, pathogenesis and management – Indian Journal of Dermatology, Venereology and Leprology

  https://ijdvl.com/nail-tic-disorders-manifestations-pathogenesis-and-management/

  Both thumb sucking and nail biting are considered to be due to difficulty in the evolution of the oral stage of a child’s psychological development. […] Higher concordance rates among monozygotic twins as compared with dizygotic twins (66% vs. 34%) suggests a genetic basis. […] Nail biters tend to have a greater frequency of obsessive-compulsive behavior. […] In persistent cases or in those with coexisting psychiatric disorders, a trial of serotonin reuptake inhibitors (SSRIs) may be attempted. […] This disorder is more of a habit and there is often no anxiety before the fingernail manipulation or any feeling of relief after the act. […] The glue is used to recreate the barrier between the proximal nail fold and nail plate thereby preventing further trauma and allowing time for the nail matrix to heal.

• #19 Frontiers | Tourette Syndrome: A Mini-Review

  https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2018.00139/full

  The cause of TS is not yet known. It is assumed that the development of the disorder is conditioned by the participation of the genetic and nongenetic (epidemiological) factors. TS belongs to polygenic hereditary disorders, where several different genes are involved in the disorder. Even though chromosomal aberrations rarely occurred in patients with TS, a clear genetic cause has not yet been revealed. The negative effects of the environment are mainly prenatal intakes (maternal stress in pregnancy, smoking, infections, fetal hypoxia) and stressful events in the child’s life. […] Tourette syndrome pathophysiological mechanisms have not yet been elucidated. Many findings are indicative of organic origin. Although tics are at least partially influenced by will, neurophysiological studies show that tics are not driven by normal motor ways designed to control free movements. Tics are not preceded by common preparatory potential (Bereitschaftspotential), and polysomnography has shown tics at various stages of sleep. Strong evidence shows changes in central neurotransmitters, especially in dopaminergic modulation. Dopamine antagonists and depleters improve tics, while drugs that augment central dopaminergic activity worsen them. The most interesting hypothesis assumes that the underlying TS is a developmental disorder leading to dopaminergic hyperinnervation of the striatum. Anatomical and functional links between the basal ganglia and the limbic system can explain the current occurrence of tics and complex behavioral problems in TS. It was proved that basal ganglia, particularly the caudatus nucleus and ventral striatolimbic complex played a significant role in the pathogenesis of OCD and primitive reproductive behavior. The influence of sex hormones on the development of these structures can explain the difference in TS among sexes, the exacerbation of puberty and estrogenic stages of the menstrual cycle, and the characteristic occurrence of complex motor and sound tics, as well as behavioral manifestations with sexual content.

• #20 The PNKD gene is associated with Tourette Disorder or Tic disorder in a multiplex family | Molecular Psychiatry

  https://www.nature.com/articles/mp2017179

  Tourette Disorder (TD) is a childhood-onset neuropsychiatric and neurodevelopmental disorder characterized by the presence of both motor and vocal tics. […] The genetic architecture of TD is believed to be complex and heterogeneous. […] A rare heterozygous nonsense mutation in PNKD was co-segregated with TD in this multiplex family. […] We concluded that reduced PNKD long isoform levels are detected in all affected individuals and we provide evidence for a mechanism whereby this might contribute to the TD phenotype. […] The etiology of TD appears to be polygenic and heterogeneous, probably involving dozens of common variants with small effect size or rare variants with larger effect size. […] A novel nonsense mutation within the paroxysmal nonkinesigenic dyskinesia (PNKD) gene was identified, which appeared to be a strong TD candidate.

• #21 The Relationship between Tourette’s Syndrome and Infections

  https://openneurologyjournal.com/VOLUME/6/PAGE/124/FULLTEXT/?doi=10.1126/sciadv.adg2248

  Increasing evidence shows that infections and an activated immune status might be involved in the pathogenesis of tic disorders. […] However, it still remains unclear what the underlying mechanism is of how infectious agents could contribute to tic symptoms. One hypothesis is that not only one particular infectious agent causes directly to the disease; instead different (chronic) infections influence the immune balance and are therefore involved in the pathology. […] Another contributing factor to the pathogenesis of these diseases could be an activation of the tryptophan catabolism through infectious agents. […] A deeper insight into the precise mechanism of how infectious agents influence immune parameter, tryptophan metabolism and the resulting neurotransmitter availability could help finding new therapeutic strategies.

• #22 Infections may cause sudden onset of tics in a child

  https://www.moleculera.com/sudden-onset-of-tics-in-child/

  Mounting evidence indicates that multiple types of infections can trigger the sudden onset of tics in a child, adolescent or adult. […] Researchers believe that in some people, common infections can trigger an abnormal immune response, in which antibodies mistakenly attack healthy cells in the brain. […] This autoimmune attack on the brain can disrupt normal neuronal cell functioning and cause inflammation in the brain, resulting in the onset of neuropsychiatric symptoms, including tics. […] Evidence points increasingly toward a role for infection and immune factors in at least a subset of Tourettes syndrome. […] For example, Group A strep infections can cause a sudden onset of tics in a child or adolescent who is genetically susceptible. […] In these cases, the child’s tics may be the result of a treatable autoimmune disorder known as Pediatric Autoimmune Neuropsychiatric Disorders Associated with Strep infections (PANDAS).

• #23 Infections may cause sudden onset of tics in a child

  https://www.moleculera.com/sudden-onset-of-tics-in-child/

  Other types of infections can trigger a sudden onset of tics in a child. […] Borrelia burgdorferi (the bacteria causing Lyme disease), mycoplasma pneumoniae, and herpes simplex virus are believed to play a role in the pathogenesis of tic disorders, such as Tourettes syndrome. […] Additionally, the enterovirus (EV) has been associated with a greater incidence of tic disorders. […] Our observations add to the growing body of literature implicating the immune-inflammatory process as relevant to the pathoetiology of some mental disorders, reports Tsai and colleagues.

• #24 The Relationship between Tourette’s Syndrome and Infections

  https://openneurologyjournal.com/VOLUME/6/PAGE/124/FULLTEXT/?doi=10.1126/sciadv.adg2248

  Taken this together, TS is a chronic relapsing disorder that can be associated with marked impairment and disability. […] The purpose of this review is to highlight our new insights into the pathophysiology of TS. We focus on the mechanisms of how infectious agents influence immune parameters, tryptophan metabolism and the resulting neurotransmitter availability. […] Therefore the characteristics of neuroinflammation need to be taken into consideration: Inflammation in the brain is characterized by activation of glial cells (mainly microglia and astrocytes) and expression of key inflammatory mediators as well as neurotoxic free radicals. […] A probable mechanism of how infections can influence the cerebral immune balance could be the activation of the tryptophan catabolism via infectious agents and elevated pro-inflammatory cytokines.

• #25 Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms | BMC Neuroscience | Full Text

  https://bmcneurosci.biomedcentral.com/articles/10.1186/1471-2202-15-6

  Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms. […] Our results confirm prior studies suggesting that tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus seem to reflect secondary compensatory mechanisms. […] In this study we used DTI to investigate microstructural integrity of white matter pathways and brain tissue in a relatively large group of unmedicated, adult patients with TS only. Our results are in line with recent findings in a small number of studies suggesting that tics are caused by alterations in prefrontal areas, thalamus and putamen. It can be hypothesized that additional changes in the cingulate gyrus are related to secondary compensatory mechanisms.

• #26 Elucidating the Nature and Mechanism of Tic Improvement in Tourette Syndrome: A Pilot Study | Tremor and Other Hyperkinetic Movements

  https://tremorjournal.org/articles/10.5334/tohm.190

  During normal brain maturation, cortical network hubs develop fewer local connections and a higher number of more distant connections. […] rs-fc-MRI studies have demonstrated that TS adolescents and adults have higher numbers of local connections and fewer distant connections—a less mature pattern of resting-state functional connectivity compared to controls. […] These findings are in agreement with recent larger studies in adolescents (ages 10-15 years) and young adults (ages 19-40) and add to a growing body of literature showing that TS is a neurodevelopmental disorder. […] Prior studies of brain connectivity in TS include findings of decreased structural connectivity (diffusion tensor imaging) in tracts involving the supplementary motor area with basal ganglia and in frontal cortico-cortical circuits.

• #27 The Dysfunctional Mechanisms Throwing Tics: Structural and Functional Changes in Tourette Syndrome

  https://www.mdpi.com/2076-328X/13/8/668

  The Dysfunctional Mechanisms Throwing Tics: Structural and Functional Changes in Tourette Syndrome […] Tourette Syndrome (TS) is a high-incidence multifactorial neuropsychiatric disorder characterized by motor and vocal tics co-occurring with several diverse comorbidities, including obsessive-compulsive disorder and attention-deficit hyperactivity disorder. […] The origin of TS is multifactorial, with strong genetic, perinatal, and immunological influences. […] Although almost all neurotransmitter systems have been implicated in TS pathophysiology, a comprehensive neurophysiological model explaining the dynamics of expression and inhibition of tics is still lacking. […] The genesis and maintenance of motor and non-motor aspects of TS are thought to arise from functional and/or structural modifications of the basal ganglia and related circuitry. […] Importantly, striatal circuits exhibit bidirectional forms of synaptic plasticity that differ in many respects from hippocampal and neocortical plasticity, including sensitivity to metaplastic molecules such as dopamine. […] TS etiology is very complex, with strong genetic influences, repeated streptococcal infections, and also pre and perinatal phenomena. […] There is accumulating evidence that immune dysregulation contributes to the pathophysiology of OCD, TS, and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). […] Importantly, blood flow and metabolism studies assessed the implication of dopaminergic transmission in the pathophysiology of TS, especially in or around portions of the caudate nucleus of the ventral striatum, a key region for motor and behavioral expression. […] TS appears to be associated with a specific cerebral network characterized by a reduction in the activity of the BG and thalamocortical circuits. […] The neural substrate established to be pathophysiological in TS relates to habit formation. […] The CSTC circuit is composed of multiple and sometimes overlapping neural pathways, and tics seem to result from dysfunctions in regions that are part of this circuit. […] Neuroimaging studies showed morphological alterations in different BG nuclei of TS patients, especially at portions of the caudate nucleus of the striatum. […] TS seems to be characterized by an excess of dopamine or supersensitivity of postsynaptic dopaminergic receptors at the BG level, resulting in an imbalance of CSCT circuits. […] The activation of the direct pathway leads to a reduction in the inhibitory activity of the GPi and the overall promotion of movement. […] In conclusion, compromised neuronal activity and enhanced dopaminergic transmission in the striatum of TS patients are thought to undermine the physiological selection of motor programs and promote their activation, thus leading to tic behavior. […] As presented in the previous paragraphs, both structural and functional anomalies of BG have been widely documented and are supposed to contribute to the induction and expression of TS. […] In the context of striatal plasticity, immunopathogenic mediators are thought to be involved in TS development, and their role might be central. […]

• #28 Tourette Syndrome and Other Tic Disorders: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1182258-overview

  Little is known about the role of the thalamus in the pathogenesis of TS. A recent study using conventional measures of volumes and surface morphology demonstrated enlargement of the thalamus of more than 5% in affected patients of all ages. These findings raise the possibility of activity-dependent hypertrophy and therefore suggest that TS may involve previously unsuspected motor pathways. […] Abnormalities of central neurotransmitters have been implicated as a cause of TS. Limited post mortem studies have shown low brainstem serotonin, low levels of glutamate in the globus pallidus, and low levels of cyclic adenosine monophosphate (AMP) in the cortex. […] Affected individuals have also been shown to have an increased rate of binding of 3H-mazindol to the presynaptic dopamine-uptake-carrier sites. This observation has led some investigators to conclude that TS results from dopaminergic hyperinnervation of the ventral striatum and associated limbic system.

• #29 What are the biological mechanisms of Tourette’s syndrome? | Paris Brain Institute

  https://parisbraininstitute.org/disease-files/tourettes-syndrome-ts/what-are-biological-mechanisms-tourettes-syndrome

  Tourettes syndrome (SGT) like many neurological diseases has a genetic component. Although not inherited, there is a genetic predisposition that increases the risk of developing the disease for a patients relatives. […] The precise mechanisms underlying the symptoms of Tourettes syndrome are still poorly understood. However, the cerebral networks connecting the cerebral cortex to deep structures, known as basal ganglia, play a key role in the genesis of tics and other related symptoms. […] Recently, a histological analysis conducted by the Yale University team suggested that the observed abnormalities may reflect a disturbed migration of GABAergic interneurons in the striatum, a key structure of the basal ganglia. […] A study conducted at the Brain Institute by Professor Yulia Worbe and her collaborators in the MOVIT team used an advanced computer analysis method to explore resting brain connectivity in people with Tourettes syndrome. The results revealed significant differences in brain networks, including the striatum, cerebellum, and insular cortex, that distinguish patients from those without the disease.

• #30 Researchers uncover mechanism controlling Tourette Syndrome tics

  https://www.nottingham.ac.uk/news/pressreleases/2013/december/researchers-uncover-mechanism-controlling-tourette-syndrome-tics.aspx

  A mechanism in the brain which controls tics in children with Tourette Syndrome (TS) has been discovered by scientists at The University of Nottingham. […] This new study is very important as it indicates that motor and vocal tics in children may be controlled by brain changes that alter the excitability of brain cells ahead of voluntary movements. […] This clinical observation suggests that there are mechanisms in the brain that are involved in controlling tics and undergo development or re-organisation during the teenage years. […] Amelia Draper added: The research is based on the general hypothesis that an area in the brain called the striatum is overactive as a result of alterations in the early development of the brain. As a result, the signals that are relayed to the brains cortex region lead to hyper-excitability and cause tics to occur.

• #31 What are the biological mechanisms of Tourette’s syndrome? | Paris Brain Institute

  https://parisbraininstitute.org/disease-files/tourettes-syndrome-ts/what-are-biological-mechanisms-tourettes-syndrome

  This work highlights the key role of brain networks in this syndrome and paves the way for the use of brain imaging to improve diagnosis and more accurately assess treatment effectiveness. […] These results shed new light on the mechanisms underlying the formation and persistence of tics, which could be partly learned actions becoming automatic, and persisting in the same way as bad habits. Alterations in certain neural networks involved in the genesis of habits may explain the exacerbation of these behaviours in patients.

• #32 The New Tics study: A Novel Approach to Pathophysiology and Cause of Tic Disorders †

  https://jpbs.hapres.com/htmls/JPBS_1245_Detail.html

  We had hypothesized that better tic suppression would predict better clinical outcomes. […] Our first publication from this project came from the first 21 children enrolled. […] We reported clinical outcomes for the New Tics children enrolled in our preliminary data. […] These results call into doubt the general assumption of complete remission for PTD. […] A larger hippocampus at baseline predicted higher tic severity at 12-month follow-up. […] These observations allow the hypothesis that greater hippocampal volume may mediate relatively inflexible habit learning, leading to greater persistence of tics between the initial assessment and the 1-year mark.

• #32 The New Tics study: A Novel Approach to Pathophysiology and Cause of Tic Disorders †

  https://jpbs.hapres.com/htmls/JPBS_1245_Detail.html

  We report on the ongoing project The New Tics Study: A Novel Approach to Pathophysiology and Cause of Tic Disorders, describing the work completed to date, ongoing studies and long-term goals. The overall goals of this research are to study the pathophysiology of Provisional Tic Disorder, and to study tic remission (or improvement) in a prospective fashion. […] Despite increasingly intensive efforts, our understanding of the etiology and pathophysiology of TS/CTD remains fragmentary. […] The present study targets just these questions. […] Importantly, this second step can be observed prospectively, minimizing the biases inherent in retrospective study designs. Equally important, studying persistence vs. remission may identify causative factors missed by studies of established TS, in which onset and persistence are confounded and often remote. Studying this earliest phase of tic disorders may revolutionize etiology, prevention or treatment.

• #33

  https://link.springer.com/article/10.1007/s00415-003-1102-4

  Tics are involuntary movements that can affect one or more muscles producing simple or complex movements. […] Blink reflex and startle reflex studies disclose an increased excitability of brainstem interneurons. […] Sensorimotor integration is abnormally processed. […] Dysfunction of basal ganglia-thalamo-cortical projections affects sensorimotor, language and limbic cortical circuits, and may explain why patients with Tourette syndrome have difficulty in inhibiting unwanted behaviors and impulses.

• #34 Dr. Danish’s Guide to Tourette Syndrome and Tic Disorders | Philadelphia Integrative Psychiatry

  https://phillyintegrative.com/blog/dr-danishs-guide-to-tourette-syndrome-and-tic-disorders

  Attention-deficit/hyperactivity disorder often co-occurs with Tourette syndrome, complicating the clinical picture and treatment approach. […] Comprehensive Behavioral Intervention for Tics (CBIT): CBIT is highly effective in reducing tics, with studies showing a 26-31% reduction in tic severity. […] Exposure and Response Prevention (ERP): This therapy gradually suppresses tics by increasing tolerance to premonitory urges. […] Clonidine has been shown to be more effective than placebo at reducing tics and is comparable to haloperidol. […] The most effective medications are antipsychotics, such as Aripiprazole, risperidone, and pimozide. […] Pramipexole, another medication commonly used for Parkinson’s disease and restless legs syndrome, has also been investigated for its potential to reduce tic severity.

• #35 Dr. Danish’s Guide to Tourette Syndrome and Tic Disorders | Philadelphia Integrative Psychiatry

  https://phillyintegrative.com/blog/dr-danishs-guide-to-tourette-syndrome-and-tic-disorders

  Tetrabenazine and deutetrabenazine have shown promise in open-label studies, although larger trials have had mixed results. […] THC and CBD compounds have shown potential in reducing tics. […] While they can sometimes worsen or even bring on tics, in some cases they are known to treat tics. […] Ecopipam: A dopamine D1-receptor antagonist showing promise in reducing tic severity, pending FDA approval. […] A review found that low-frequency rTMS targeting the supplementary motor area (SMA) was particularly effective, with approximately 62.5% of OCD studies and 85.7% of TD studies showing significant clinical improvements. […] tDCS involves applying a low electrical current to the brain, showing significant reductions in tic severity in some studies. […] DBS is a promising treatment for severe, treatment-refractory Tourette syndrome.

• #36 Orofacial Motor Tics

  https://ostrowonline.usc.edu/orofacial-motor-tics/

  Rather than a voluntary movement, a tic is a movement which relieves a voluntary urge, and this is the key characteristic which differentiates a tic from another movement disorder. […] The cortico-basal ganglia pathway is involved in normal motor control and implicated in multiple movement disorders, so a dysfuntion of this area will produce brief, repetitive muscle contractions. […] The most common and severe form of a multiple tic disorder is Tourettes syndrome, which includes motor and vocal tics. This condition has been related with abnormalities within cerebro-basal ganglia circuits. […] If there is no actual change in the cerebro-basal circuits, some tics might be subject to voluntary inhibitory control. […] Motor inhibition and attentional processing are tightly linked and both processes might rely on similar cognitive and neural mechanisms, providing the basis for tics inhibition with behavioral therapy. […] The blockade of the striatal dopamine-D2 receptors with dopamine receptor antagonists produces a tic-reducing effect. […] It has been proposed that if the alterations of methylation levels of dopaminergic genes are controlled, there will be a reduction of spontaneous fluctuations of tics.

• #37 Researchers uncover mechanism controlling Tourette Syndrome tics | ScienceDaily

  https://www.sciencedaily.com/releases/2013/12/131211104127.htm

  If there is a relationship between this cortical excitability or hyperactivity and tics then this is really important as it means that there may be something that we might be able to do to help children with TS to better control these unwanted movements. […] Early results suggest that TDS can be applied to decrease neuronal excitability and this may be effective in suppressing tics for extended periods. […] For the one-third of people who aren’t going to get better this could offer them a much needed assistance with controlling their tics, while relying less on other conventional pharmaceutical therapies which can have associated side effects such as weight gain or tiredness.

• #38 Neurobiology of Tourette Syndrome: Current Status and Need for Further Investigation | Journal of Neuroscience

  https://www.jneurosci.org/content/31/35/12387

  Numerous neurotransmitters (dopamine, glutamate, GABA, serotonin, acetylcholine, norepinephrine, and opiates) are involved in the transmission of messages through CSTC circuits, and each has been proposed as a potential pathophysiologic mechanism. […] Dopamine dysfunction is considered a prime abnormality in TS based on tic suppression with the use of dopamine antagonists (antipsychotics), results from various nuclear imaging protocols, CSF analysis, and postmortem studies. […] Recognizing the various clinical manifestations seen in TS, it is highly likely that this disorder involves a dysfunction of more than one neurotransmitter system or a second messenger defect. […] In summary, further investigations are required to identify the underlying biochemical defect in this complex disorder.

• #39 TS Research Breakthrough: Scientists Undercover Mechanism Controlling Tics – Tourette Canada

  https://tourette.ca/2023/05/ts-research-breakthrough-scientists-undercover-mechanism-controlling-tics/

  Scientists have discovered a mechanism that controls Tourette Syndrome tics. […] Understanding the relationship between the cortical excitability and tics means that scientists may be able to help children better control their tics, says Professor Jackson. […] Early results suggested that this type of brain stimulation may help to reduce the excitability which leads to tics, thus helping individuals to have long tic-free periods. […] The hope is that the technology used in the study can be made into a cheap and portable device that can be applied to children while they are at home. The device would then help the children to control their tics and make their control more effective.

• #40 The New Tics study: A Novel Approach to Pathophysiology and Cause of Tic Disorders †

  https://wap.hapres.com/htmls/JPBS_1245_Detail.html

  We now have 12-month outcome data on 63 children with New Tics. We have discovered fascinating clinical results, and are beginning to identify biological predictors of outcome. […] The clearest benefits are that it may identify entirely new directions for further etiologic and pathophysiological research, and it can clarify the causality of associations we find. […] The New Tics population is also important in its own right. […] The proposed work takes preliminary but necessary steps toward that possibility. […] If we understood those mechanisms better—if we knew why tics improve in many of these children—we could hope to design rational, mechanism-based treatments for patients who do have persistent tics. […] We hypothesized that specific features would differentiate the New Tics participants from tic-free controls, and predict worse outcome at the one-year anniversary of tic onset.

• #41 Neurobiology of Tourette Syndrome: Current Status and Need for Further Investigation | Journal of Neuroscience

  https://www.jneurosci.org/content/31/35/12387

  Tourette syndrome (TS) is a common, chronic neuropsychiatric disorder characterized by the presence of fluctuating motor and phonic tics. […] Evidence supports TS being an inherited disorder; however, the precise genetic abnormality remains unknown. Pathologic involvement of cortico-striatal-thalamo-cortical (CSTC) pathways is supported by neurophysiological, brain imaging, and postmortem studies, but results are often confounded by small numbers, age differences, severity of symptoms, comorbidity, use of pharmacotherapy, and other factors. […] Nevertheless, despite multiple advances and widespread acceptance of TS being a biological disorder, the precise etiology and underlying pathophysiological mechanisms remain unknown. […] The primary site of abnormality remains controversial. Although numerous neurotransmitters participate in the transmission of messages through CSTC circuits, a dopaminergic dysfunction is considered a leading candidate.

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