J Clin Neurol.  2015 Apr;11(2):122-131. 10.3988/jcn.2015.11.2.122.

Chasing Tics in the Human Brain: Development of Open, Scheduled and Closed Loop Responsive Approaches to Deep Brain Stimulation for Tourette Syndrome

• Almeida L
• Martinez-Ramirez D
• Rossi PJ
• Peng Z
• Gunduz A
• Okun MS

• KMID: 2242656
• DOI: http://doi.org/10.3988/jcn.2015.11.2.122

Abstract

Tourette syndrome is a childhood-onset disorder characterized by a combination of motor and vocal tics, often associated with psychiatric comorbidities including attention deficit and hyperactivity disorder and obsessive-compulsive disorder. Despite an onset early in life, half of patients may present symptoms in adulthood, with variable degrees of severity. In select cases, the syndrome may lead to significant physical and social impairment, and a worrisome risk for self injury. Evolving research has provided evidence supporting the idea that the pathophysiology of Tourette syndrome is directly related to a disrupted circuit involving the cortex and subcortical structures, including the basal ganglia, nucleus accumbens, and the amygdala. There has also been a notion that a dysfunctional group of neurons in the putamen contributes to an abnormal facilitation of competing motor responses in basal ganglia structures ultimately underpinning the generation of tics. Surgical therapies for Tourette syndrome have been reserved for a small group of patients not responding to behavioral and pharmacological therapies, and these therapies have been directed at modulating the underlying pathophysiology. Lesion therapy as well as deep brain stimulation has been observed to suppress tics in at least some of these cases. In this article, we will review the clinical aspects of Tourette syndrome, as well as the evolution of surgical approaches and we will discuss the evidence and clinical responses to deep brain stimulation in various brain targets. We will also discuss ongoing research and future directions as well as approaches for open, scheduled and closed loop feedback-driven electrical stimulation for the treatment of Tourette syndrome.

Keyword

deep brain stimulation; Tourette syndrome; tics; closed-loop brain stimulation

MeSH Terms

Amygdala
Basal Ganglia
Brain*
Comorbidity
Deep Brain Stimulation*
Electric Stimulation
Humans
Neurons
Nucleus Accumbens
Obsessive-Compulsive Disorder
Putamen
Tics*
Tourette Syndrome*

Figure

• 

  Fig. 1 Summary of the proposed targets for DBS in Tourette syndrome. A: The thalamus in a coronal view, wherein the centromedian-parafascicular (CM-pf) complex is targeted. B: A cross-sectional view of the thalamus in detail, demonstrating the anatomical relation of the CM nucleus with the anterior portion of the ventralis oralis (VOA) nucleus, targeted by additional coagulations during the initial thalamotomy studies. C: Different areas of globus pallidus interna (GPi) that have been targeted, and D: A less studied, although with some reports of satisfactory clinical response, the anterior limb of internal capsule (AIC) and nucleus accumbens (NA). DBS: deep brain stimulation, GPe: globus palidus externa, SN: substantia nigra pars reticulata, STN: subthalamic nucleus, VOP: posterior portion of the ventralis oralis.

• 

  Fig. 2 Summary of the proposed approaches for DBS in Tourette syndrome. A: The conventional stimulation in an open loop fashion currently used widely in movement disorders, where energy is continuously delivered to a target, with parameters set by a clinician. B: The concept of closed loop DBS, where energy is delivered as a real time feedback response to physiological changes detected by LFPs through a computer interface. C: An alternative mode of closed loop DBS, in which energy is delivered as a real time feedback to changes in the surface of the brain, detected by EEG and/or ECoG. D: The novel concept of neural network stimulation, where the stimulation is delivered in a feedback response to a physiological changes detected at the cortical level through EEG and ECoG and subcortical level detected by LFPs, yielding delivery of electrical stimulation through both the DBS and ECoG leads. DBS: deep brain stimulation, ECoG: electrocorticography, EEG: electroencephalogram, LFP: local field potential.

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