Deep brain stimulation and sensorimotor gating in tourette syndrome and obsessive-compulsive disorder

The environment surrounding an individual causes a flood of stimuli, which are filtered in the brain with a mechanism called sensorimotor gating (SG), to ensure that only relevant information reaches consciousness. An important mechanism in this process is the startle reflex. Prepulse inhibition is a scientific tool to measure the reduction of the startle reflex that is induced by a prior sensory warning signal and can be stated in percent. The mechanism of SG and PPI are discussed to cross brain pathways in functional loops starting in the cortex, passing on to the striatum, to the thalamus and returning to the cortex (CSTC-loops). Researchers suggests that in Tourette-Syndrome (TS) and Obsessive-Compulsive-Disorder (OCD), these pathways are dysregulated (Schleyken et al. 2020). Thus, the question arose if abnormal SG can be detected in patients with TS and OCD and how the neuromodulative treatment with deep brain stimulation (DBS) influences SG (Schleyken et al. 2020). The study underlying this dissertation investigated changes of PPI of the acoustic startle reflex by DBS of the thalamic nuclei and the anterior limb of the internal capsule nucleus accumbens respectively, and included 10 patients with TS, 8 patients with OCD and 18 healthy controls, who matched in age and gender (Schleyken et al. 2020). Patients were measured twice, during active stimulation (ON-condition) and when the stimulation was switched off (OFF-condition), and randomization of the order of condition was used to enhance reliability (Schleyken et al. 2020). We found no significant difference in PPI (measured in percent) between the ON- and OFF- condition in patients with TS as well as patients with OCD. Yet, the analysis revealed significantly reduced PPI levels of patients with TS in the ON-condition compared to healthy controls. However, the comparison did not reach significance for the OFF-condition (Schleyken et al. 2020). As DBS is still a rare treatment in psychiatric diseases, a small sample size limits our results. Furthermore, nicotine and psychoactive medication have been shown to influence PPI levels but were not controlled for in our study. DBS includes an operative neurosurgical procedure, but we did not collect PPI data before the surgical procedure took place so that we were not able to assess any data of long-term stimulation effect (Schleyken et al. 2020). Keeping these limitations in mind, the main finding of our study was that PPI is altered in patients with TS which is supported by research results to date. However, our results differ from our previously published data where we found significantly reduced PPI levels in patients with OCD. As the exact effect of deep brain stimulation on cortical functions remains unknown, we suggest further research to disentangle its potentials and limitations (Schleyken et al. 2020)

Deep brain stimulation and sensorimotor gating in tourette syndrome and obsessive-compulsive disorder

Recent translational data suggest that deep brain stimulation (DBS) of the cortico-striato-thalamo-cortical (CSTC) loops improves sensorimotor gating in psychiatric disorders that show deficient prepulse inhibition (PPI), a robust operational measure of sensorimotor gating. To our knowledge we are the first to investigate this effect in patients with Tourette syndrome (TS). We measured PPI of the acoustic startle reflex in patients with TS (N = 10) or Obsessive-Compulsive Disorder (OCD) (N = 8) treated with DBS of the centromedian and ventro-oral internal thalamic nucleus and the anterior limb of internal capsule-nucleus accumbens area respectively, and aged- and gender-matched healthy controls (HC). PPI of the DBS groups was measured in randomized order in the ON and OFF stimulation condition. Statistical analysis revealed no significant difference in PPI (%) of patients with TS between ON (M = 20.5, SD = 14.9) and OFF (M = 25.2, SD = 29.7) condition. There were significantly reduced PPI levels in patients with TS in the ON condition compared to HC (M = 49.2, SD = 10.7), but no significant difference in PPI between TS in the OFF condition and HC. Furthermore, we found no significant stimulation or group effect for OCD and HC (OCD ON: M = 57.0, SD = 8.3; OCD OFF: 67.8, SD = 19.6; HC: M = 63.0, SD = 24.3). Our study has a number of limitations. Sample sizes are small due to the restricted patient collective. The study was not controlled for use of psychoactive medication or nicotine. Furthermore, we were not able to assess presurgical PPI measurements. In conclusion, we were able to show that PPI is impaired in patients with TS. This finding is in line with recent translational work. With respect to the OCD cohort we were not able to replicate our previously published data. A disability in sensorimotor gating plays a pivotal role in many psychiatric disorders therefore more research should be conducted to disentangle the potential and limitations of modulating sensorimotor gating via brain stimulation techniques

Thalamic deep brain stimulation for Tourette Syndrome: A naturalistic trial with brief randomized, double-blinded sham-controlled periods

Background: There is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome. Objectives: In this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation. Methods: We included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six-and twelve-months' assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety. Results: Active stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae. Conclusion: Our results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Patients with isolated REM-sleep behavior disorder have elevated levels of alpha-synuclein aggregates in stool

Abstract Misfolded and aggregated α-synuclein is a neuropathological hallmark of Parkinson’s disease (PD). Thus, α-synuclein aggregates are regarded as a biomarker for the development of diagnostic assays. Quantification of α-synuclein aggregates in body fluids is challenging, and requires highly sensitive and specific assays. Recent studies suggest that α-synuclein aggregates may be shed into stool. We used surface-based fluorescence intensity distribution analysis (sFIDA) to detect and quantify single particles of α-synuclein aggregates in stool of 94 PD patients, 72 isolated rapid eye movement sleep behavior disorder (iRBD) patients, and 51 healthy controls. We measured significantly elevated concentrations of α-synuclein aggregates in stool of iRBD patients versus those of controls (p = 0.024) or PD patients (p < 0.001). Our results show that α-synuclein aggregates are excreted in stool and can be measured using the sFIDA assay, which could support the diagnosis of prodromal synucleinopathies