A Primary Role for Nucleus Accumbens and Related Limbic Network in Vocal Tics

McCairn, Kevin W.; Nagai, Yuji; Hori, Yukiko; Ninomiya, Taihei; Kikuchi, Erika; Lee, Juyoung; Suhara, Tetsuya; Iriki, Atsushi; Minamimoto, Takafumi; Takada, Masahiko; Isoda, Masaki; Matsumoto, Masayuki

doi:10.1016/j.neuron.2015.12.025

Cited by 63 publications

(61 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unlike basal ganglia diseases which are associated with impairment of involuntary movement, cerebellar disorders are associated with failing of voluntary movement. The role of the cerebellum in the pathophysiology of GTS was most recently supported in an investigation in which vocal and motor tics were induced by focal disruption in ventral and motor striatum, respectively (McCairn et al 2016). Interestingly, metabolic observations in those experiments also implicated the hippocampus and amygdala, although the other subcortical nuclei of the CBGTC were not associated.…”

Section: Anatomy and Pathophysiologymentioning

confidence: 96%

“…An investigation which also employed [ 15 O] H 2 O PET in which vocal and motor tics were induced in non-human primates reported a much smaller network with different activated brain regions (McCairn et al 2016). Injection of the GABA antagonist bicuculline into the NA or dorsolateral sensorimotor putamen produced repetitive complex vocalizations or motor tics in the orofacial and/or the arm region, respectively.…”

Section: Anatomy and Pathophysiologymentioning

confidence: 99%

See 1 more Smart Citation

Putting the Pieces Together in Gilles de la Tourette Syndrome: Exploring the Link Between Clinical Observations and the Biological Basis of Dysfunction

2016

View full text Add to dashboard Cite

Gilles de la Tourette syndrome is a complex, idiopathic neuropsychiatric disorder whose pathophysiological mechanisms have yet to be elucidated. It is phenotypically heterogeneous and manifests more often than not with both motor and behavioral impairment, although tics are its clinical hallmark. Tics themselves present with a complex profile as they characteristically wax and wane and are often preceded by premonitory somatosensory sensations to which it is said a tic is the response. Highly comorbid with obsessive–compulsive disorder and attention deficit-hyperactivity disorder, it is purported to be an epigenetic, neurodevelopmental spectrum disorder with a complex genetic profile. It has a childhood onset, occurs disproportionately in males, and shows spontaneous symptomatic attenuation by adulthood in the majority of those afflicted. Although not fully understood, its neurobiological basis is linked to dysfunction in the cortico-basal ganglia–thalamo–cortical network. Treatment modalities for Tourette syndrome include behavioral, pharmacological and surgical interventions, but there is presently no cure for the disorder. For those severely affected, deep brain stimulation (DBS) has recently become a viable therapeutic option. A key factor to attaining optimal results from this surgery is target selection, a topic still under debate due to the complex clinical profile presented by GTS patients. Depending on its phenotypic expression and the most problematic aspect of the disorder for the individual, one of three brain regions is most commonly chosen for stimulation: the thalamus, globus pallidus, or nucleus accumbens. Neurophysiological analyses of intra- and post-operative human electrophysiological recordings from clinical DBS studies suggest a link between tic behavior and activity in both the thalamus and globus pallidus. In particular, chronic recordings from the thalamus have shown a correlation between symptomatology and (1) spectral activity in gamma band power and (2) theta/gamma cross frequency coherence. These results suggest gamma oscillations and theta/gamma cross correlation dynamics may serve as biomarkers for dysfunction. While acute and chronic recordings from human subjects undergoing DBS have provided better insight into tic genesis and the neuropathophysiological mechanisms underlying Tourette syndrome, these studies are still sparse and the field would greatly benefit from further investigations. This review reports data and discoveries of scientific and clinical relevance from a wide variety of methods and provides up-to-date information about our current understanding of the pathomechanisms underlying Tourette syndrome. It gives a comprehensive overview of the current state of knowledge and addresses open questions in the field.

show abstract

Section: Anatomy and Pathophysiologymentioning

confidence: 96%

Section: Anatomy and Pathophysiologymentioning

confidence: 99%

Putting the Pieces Together in Gilles de la Tourette Syndrome: Exploring the Link Between Clinical Observations and the Biological Basis of Dysfunction

2016

View full text Add to dashboard Cite

show abstract

“…Over the past two decades, DBS has been used as a promising treatment option for medication refractory and severely affected patients with TS 6–8. Evidence from neuroimaging,9–11 stereotactic lesions12–14 and animal models15–17 have collectively demonstrated that the thalamo-striatal-cortical circuit18 is involved in the pathophysiology of TS. Based on these findings, thalamic and pallidal nuclei in the circuits have been selected as DBS targets for the treatment of TS.…”

Section: Introductionmentioning

confidence: 99%

Differentiating tic electrophysiology from voluntary movement in the human thalamocortical circuit

Cagle

Okun

Opri

et al. 2020

J Neurol Neurosurg Psychiatry

View full text Add to dashboard Cite

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.

show abstract

“…A face-valid animal model of tics has been a very important but elusive goal 33 . McCairn and colleagues have now published their important work characterizing a nonhuman primate tic model 34 . Temporary unilateral disinhibition of the nucleus accumbens (NA)—the ventral, more limbic-connected part of the striatum—produces vocalizations in monkeys that resemble vocal tics in human patients.…”

Section: Resultsmentioning

confidence: 99%