Neurobiological Substrates of Tourette's Disorder

Leckman, James F.; Bloch, Michael H.; Smith, Megan; Larabi, Daouia; Hampson, Michelle

doi:10.1089/cap.2009.0118

Cited by 169 publications

(131 citation statements)

References 112 publications

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“…203,206 Individuals with TS have demonstrated structural and functional abnormalities within the corticostriatothalamocortical loop, 261,302 although the primary site of abnormality remains controversial. 65 In fact, imaging studies in individuals with TS reveal widespread abnormalities in the size, connectivity, and microstructure of the caudate nucleus, 158,222 thalamus, 174 sensorimotor and prefrontal cortex, 268 cerebellum, 277 corpus callosum, 41 amygdala and hippocampus, 221 and limbic structures such as the amygdalae and NAcc. 207 Electrophysiological studies implicate overexcitability and dysregulation of frontal-subcortical circuitry resulting in deficiencies in processing of stimuli.…”

Section: Tourette Syndrome Backgroundmentioning

confidence: 99%

Deep brain stimulation for psychiatric disorders: where we are now

Cleary

Ozpinar

Raslan

et al. 2015

FOC

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Fossil records showing trephination in the Stone Age provide evidence that humans have sought to influence the mind through physical means since before the historical record. Attempts to treat psychiatric disease via neurosurgical means in the 20th century provided some intriguing initial results. However, the indiscriminate application of these treatments, lack of rigorous evaluation of the results, and the side effects of ablative, irreversible procedures resulted in a backlash against brain surgery for psychiatric disorders that continues to this day. With the advent of psychotropic medications, interest in invasive procedures for organic brain disease waned. Diagnosis and classification of psychiatric diseases has improved, due to a better understanding of psychiatric patho-physiology and the development of disease and treatment biomarkers. Meanwhile, a significant percentage of patients remain refractory to multiple modes of treatment, and psychiatric disease remains the number one cause of disability in the world. These data, along with the safe and efficacious application of deep brain stimulation (DBS) for movement disorders, in principle a reversible process, is rekindling interest in the surgical treatment of psychiatric disorders with stimulation of deep brain sites involved in emotional and behavioral circuitry. This review presents a brief history of psychosurgery and summarizes the development of DBS for psychiatric disease, reviewing the available evidence for the current application of DBS for disorders of the mind.

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Section: Tourette Syndrome Backgroundmentioning

confidence: 99%

Deep brain stimulation for psychiatric disorders: where we are now

Cleary

Ozpinar

Raslan

et al. 2015

FOC

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“…A series of parallel cortico-striatal-thalamocortical (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 Leckman et al, 2010;Mazzone et al, 2010). In classical models of movement disorders the basal ganglia was believed to influence behavior by changing cortical excitability through the interplay of the "direct" [striatum to globus pallidus interna (GPi)] and the multisynaptic "indirect" [striatum to globus pallidus externa (GPe) to subthalamic nucleus (STN) to GPi] pathway (Albin et al, 1989).…”

Section: Circuitsmentioning

confidence: 99%

Neurobiology of Tourette Syndrome: Current Status and Need for Further Investigation: Table 1.

Felling¹,

Singer²

2011

J. Neurosci.

198

116

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Tourette syndrome (TS) is a common, chronic neuropsychiatric disorder characterized by the presence of fluctuating motor and phonic tics. The typical age of onset is ϳ5-7 years, and the majority of children improve by their late teens or early adulthood. Affected individuals are at increased risk for the development of various comorbid conditions, such as obsessive-compulsive disorder, attention deficit hyperactivity disorder, school problems, depression, and anxiety. There is no cure for tics, and symptomatic therapy includes behavioral and pharmacological approaches. 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. 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. Several animal models have been used to study behaviors similar to tics as well as to pursue potential pathophysiological deficits. TS is a complex disorder with features overlapping a variety of scientific fields. Despite description of this syndrome in the late 19th century, there remain numerous unanswered neurobiological questions.In the 1880's, Georges Gilles de la Tourette published a two-part article in which he emphasized differences between tics and chorea. Although many of the descriptions about the disorder, which now bears his name [Tourette syndrome (TS)], have been revised, his belief that tics are a neurological movement disorder and not a psychiatric condition persists to the present (Goetz and Klawans, 1982). Nevertheless, despite multiple advances and widespread acceptance of TS being a biological disorder, the precise etiology and underlying pathophysiological mechanisms remain unknown. The goals of the present review are to briefly describe the clinical phenomenology of TS and related tic disorders, to review current information on genetic and neurobiological mechanisms, and to identify areas in need of further investigation.

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“…Convergent evidence implicates the corticobasal ganglia circuitry in the pathophysiology of TS, although details remain poorly understood (12,13). The input nucleus of the basal ganglia, the striatum, receives glutamatergic projections from the cortex and thalamus.…”

mentioning

confidence: 99%

“…The input nucleus of the basal ganglia, the striatum, receives glutamatergic projections from the cortex and thalamus. The striatum is reduced in volume in individuals with TS (12)(13)(14), and this reduction predicts the severity and the persistence of symptoms (15). Whereas the cellular architecture of the dorsal striatum is fairly uniform throughout its medial-lateral extent, the topographic organization of cortical afferents leads to functional segregation among subregions (16)(17)(18)(19).…”

mentioning

confidence: 99%

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

Xu¹,

Kobets²,

Du³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

144

164

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Gilles de la Tourette syndrome (TS) is characterized by tics, which are transiently worsened by stress, acute administration of dopaminergic drugs, and by subtle deficits in motor coordination and sensorimotor gating. It represents the most severe end of a spectrum of tic disorders that, in aggregate, affect ∼5% of the population. Available treatments are frequently inadequate, and the pathophysiology is poorly understood. Postmortem studies have revealed a reduction in specific striatal interneurons, including the large cholinergic interneurons, in severe disease. We tested the hypothesis that this deficit is sufficient to produce aspects of the phenomenology of TS, using a strategy for targeted, specific cell ablation in mice. We achieved ∼50% ablation of the cholinergic interneurons of the striatum, recapitulating the deficit observed in patients postmortem, without any effect on GABAergic markers or on parvalbuminexpressing fast-spiking interneurons. Interneuron ablation in the dorsolateral striatum (DLS), corresponding roughly to the human putamen, led to tic-like stereotypies after either acute stress or D-amphetamine challenge; ablation in the dorsomedial striatum, in contrast, did not. DLS interneuron ablation also led to a deficit in coordination on the rotorod, but not to any abnormalities in prepulse inhibition, a measure of sensorimotor gating. These results support the causal sufficiency of cholinergic interneuron deficits in the DLS to produce some, but not all, of the characteristic symptoms of TS.Tourette sydrome | basal ganglia | interneurons | acetylcholine | animal models

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Neurobiological Substrates of Tourette's Disorder

Cited by 169 publications

References 112 publications

Deep brain stimulation for psychiatric disorders: where we are now

Deep brain stimulation for psychiatric disorders: where we are now

Neurobiology of Tourette Syndrome: Current Status and Need for Further Investigation: Table 1.

Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome

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