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

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.

Increased thalamic gamma band activity correlates with symptom relief following deep brain stimulation in humans with Tourette's syndrome.

Tourette syndrome (TS) is an idiopathic, childhood-onset neuropsychiatric disorder, which is marked by persistent multiple motor and phonic tics. The disorder is highly disruptive and in some cases completely debilitating. For those with severe, treatment-refractory TS, deep brain stimulation (DBS) has emerged as a possible option, although its mechanism of action is not fully understood. We performed a longitudinal study of the effects of DBS on TS symptomatology while concomitantly examining neurophysiological dynamics. We present the first report of the clinical correlation between the presence of gamma band activity and decreased tic severity. Local field potential recordings from five subjects implanted in the centromedian nucleus (CM) of the thalamus revealed a temporal correlation between the power of gamma band activity and the clinical metrics of symptomatology as measured by the Yale Global Tic Severity Scale and the Modified Rush Tic Rating Scale. Additional studies utilizing short-term stimulation also produced increases in gamma power. Our results suggest that modulation of gamma band activity in both long-term and short-term DBS of the CM is a key factor in mitigating the pathophysiology associated with TS.