Dataset Information

Brain mechanisms for prepulse inhibition in adults with Tourette syndrome: initial findings.

ABSTRACT: Prepulse inhibition (PPI) of the startle reflex is disrupted in a number of developmental neuropsychiatric disorders, including Tourette syndrome (TS). This disruption is hypothesized to reflect abnormalities in sensorimotor gating. We applied whole-brain functional magnetic resonance imaging (fMRI) to elucidate the neural correlates of PPI in adult TS subjects using airpuff stimuli to the throat to elicit a tactile startle response. We used a cross-sectional, case-control study design and a blocked-design fMRI paradigm. There were 33 participants: 17 with TS and 16 healthy individuals. As a measure of PPI-related brain activity, we looked for differential cerebral activation to prepulse-plus-pulse stimuli versus activation to pulse-alone stimuli. In healthy subjects, PPI was associated with increased activity in multiple brain regions, of which activation in the left middle frontal gyrus in the healthy controls showed a significant linear correlation with the degree of PPI measured outside of the magnet. Group comparisons identified nine regions where brain activity during PPI differed significantly between TS and healthy subjects. Among the TS subjects, activation in the left caudate was significantly correlated with current tic severity as measured by the total score on the Yale Global Tic Severity Scale. Differential activation of the caudate nucleus associated with current tic severity is consistent with neuropathological data and suggests that portions of cortical-striatal circuits may modulate the severity of tic symptoms in adulthood.

SUBMITTER: Zebardast N

PROVIDER: S-EPMC3932431 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Brain mechanisms for prepulse inhibition in adults with Tourette syndrome: initial findings.

Zebardast Nazlee N Crowley Michael J MJ Bloch Michael H MH Mayes Linda C LC Wyk Brent Vander BV Leckman James F JF Pelphrey Kevin A KA Swain James E JE

Psychiatry research 20130731 1

Prepulse inhibition (PPI) of the startle reflex is disrupted in a number of developmental neuropsychiatric disorders, including Tourette syndrome (TS). This disruption is hypothesized to reflect abnormalities in sensorimotor gating. We applied whole-brain functional magnetic resonance imaging (fMRI) to elucidate the neural correlates of PPI in adult TS subjects using airpuff stimuli to the throat to elicit a tactile startle response. We used a cross-sectional, case-control study design and a blo ...[more]

PMID: 23916249

Similar Datasets

Project description:Tourette syndrome is a chronic tic disorder characterized by motor and vocal tics. Comorbidities such as attention deficit hyperactivity disorder and obsessive compulsive disorder can be found. The overlap between neuroanatomical regions and neurotransmitter systems in the olfactory system and the pathophysiology of Tourette syndrome let us hypothesize altered olfactory performance in Tourette syndrome. The main objective of this study was to systematically assess olfactory functioning in subjects with Tourette syndrome and to compare it to healthy controls. We assessed 28 adults with Tourette syndrome (age 33.1±9.4 years, disease duration 23.7±9.7 years) and 28 healthy controls (age 32.9±9.0 years) matched in regard to age, sex, education and smoking habits. The "Sniffin Sticks" test battery was applied to assess odor threshold, discrimination, and identification. Additionally, the combined score of the odor threshold test, the odor discrimination test and the odor identification test of the "Sniffin Sticks" test battery was calculated. Although it was not the primary aim of this study, we assessed whether tics and comorbidity could contribute to olfactory alterations in adults with Tourette syndrome. Therefore, clinical scores were used to assess severity of tics and co-morbidity such as attention deficit hyperactivity disorder, obsessive compulsive disorder, anxiety and depression in subjects with Tourette syndrome. Pathology of the nasal cavities was excluded with rhinoendoscopy. Independent sample t-tests were applied to compare performance in olfactory tests. In the case of statistically significant differences (critical p-value: 0.05), multiple linear regression analysis was carried out to explore whether tic severity, social impairment, co-morbidity or medical treatment had an impact on the differences found. Descriptive values are reported as mean ± standard deviation. Tourette syndrome subjects showed lower combined scores (Tourette syndrome subjects 31.9 ± 5.1 versus healthy controls 35.0 ± 3.1; p = 0.007), odor identification scores (Tourette syndrome subjects 12.4 ± 2.0 versus healthy controls 13.7 ± 1.4; p = 0.008) and odor discrimination scores (Tourette syndrome subjects 12.1 ± 2.1 versus healthy controls 13.2 ± 1.6; p = 0.041) in comparison to healthy subjects, while there was no difference in odor threshold (Tourette syndrome subjects 7.3 ± 2.7 versus healthy controls 8.1 ± 2.2; p = 0.22). Seven out of 28 Tourette syndrome subjects (25%) scored in the range of the age- and sex-dependent combined score for hyposmia, while two of 28 healthy controls (7%) had a similar low combined score. None of the participants were found to have functional anosmia. Multiple linear regression analyses suggest that social impairment may a predictor for low combined score and odor identification score in Tourette syndrome subjects (p = 0.003). Compared to healthy controls, altered olfaction in adults with Tourette syndrome was found in this study. Normal odor threshold level but lower scores at tasks involving supra-threshold odor concentrations point towards a central-nervous alteration in the processing of olfactory information in Tourette syndrome.

Project description:Abstract Background: Prepulse inhibition (PPI) is a measure of sensorimotor gating shown to be disrupted in schizophrenia. Since dysfunctions of the catecholamine signaling in the cortical circuitry has been associated with reduced PPI, associations between PPI and gene mutations involved in these signaling pathways need to be investigated. The catechol-O-methyltransferase (COMT) Val158Met single nucleotide polymorphism (SNP), which leads to lower COMT enzyme activity in dorsolateral prefrontal cortex of Met/Met carriers, has been shown to modulate PPI disruptions, with higher PPI associated with greater Met load in healthy subjects and schizophrenia patients. Interaction effects with functional SNPs on other catecholamine-related genes, namely norepinephrine transporter (NET), dopamine transporter (DAT), monoamine oxidase A (MAOA), and D2 receptor (DRD2), will shed more light on the specific way in which Val158Met SNP might influence PPI. The current study investigates (1) the association of the Val158Met SNP with PPI; and (2) interaction effects between the Val158Met SNP and other catecholamine-related SNPs. Methods: The Marine Resiliency Study (MRS) is a longitudinal study involving 2593 male active duty Marines recruited in Southern California, and participating in the study before deployment (1 month), and after deployment (1 week, 3 and 6 months). Acoustic startle reflex and PPI were measured on all visits after deployment however only the first visit data will be presented here. Exclusion criteria included low signal to noise, recent traumatic brain injury, poor hearing, inadequate habituation, and non-Caucasian ethnicity. 1193 subjects were included in the final analysis. Results: Following a 2-way ANOVA with the Val158Met SNP (rs4680) as between-subject and interstimulus interval (ISI) as within-subject factors, and controlling for population admixture, no main effect or interaction on PPI was found. For each of the other catecholamine-related SNPs, 3-way ANOVAs with ISI as within-subject factor and Val158Met SNP and the other candidate SNP as between-subject factors were conducted. For the DAT SNP (rs27072), a significant Val158Met SNP × DAT SNP × ISI interaction was found. However, this interaction effect does not survive correction for multiple comparisons and was found only for the ISI = 30 ms condition, not for the other 2 (60 ms and 120 ms), suggesting a type I error. Neither main effect nor interaction with Val158Met SNP was found for the DRD2 (rs1800497), MAOA (rs6323), and NET (rs28386840) SNPs. Conclusion: Despite sufficient power and sample size in the current study, the association between the Val158Met SNP and PPI reported in previous human studies has not been replicated. Also, no interaction effect was found between Val158Met and other candidate SNPs that influence catecholamine signaling. Further investigation will determine if the Val158Met effects on PPI are modulated by trauma history.

Project description:ContextTics in Tourette syndrome begin in childhood, peak in early adolescence, and often decrease by early adulthood. However, some adult patients continue to have impairing tics. Medications for tics are often effective but can cause adverse effects. Behavior therapy may offer an alternative but has not been examined in a large-scale controlled trial in adults.ObjectiveTo test the efficacy of a comprehensive behavioral intervention for tics in adults with Tourette syndrome of at least moderate severity.DesignA randomized controlled trial with posttreatment evaluations at 3 and 6 months for positive responders.SettingThree outpatient research clinics.PatientsPatients (N = 122; 78 males; age range, 16-69 years) with Tourette syndrome or chronic tic disorder were recruited between December 27, 2005, and May 21, 2009.InterventionsPatients received 8 sessions of comprehensive behavioral intervention for tics or 8 sessions of supportive treatment for 10 weeks. Patients with a positive response were given 3 monthly booster sessions.Main outcome measuresTotal tic score on the Yale Global Tic Severity Scale and the Clinical Global Impression-Improvement scale rated by a clinician masked to treatment assignment.ResultsBehavior therapy was associated with a significantly greater mean (SD) decrease on the Yale Global Tic Severity Scale (24.0 [6.47] to 17.8 [7.32]) from baseline to end point compared with the control treatment (21.8 [6.59] to 19.3 [7.40]) (P < .001; effect size = 0.57). Twenty-four of 63 patients (38.1%) were rated as much improved or very much improved on the Clinical Global Impression-Improvement scale compared with 4 of 63 (6.4%) in the control group (P < .001). Attrition was 13.9%, with no difference across groups. Patients receiving behavior therapy who were available for assessment at 6 months after treatment showed continued benefit.ConclusionComprehensive behavior therapy is a safe and effective intervention for adults with Tourette syndrome.Trial registrationclinicaltrials.gov Identifier: NCT00231985.

Project description:Tourette syndrome is a childhood-onset neuropsychiatric disorder with a high prevalence of attention deficit hyperactivity and obsessive-compulsive disorder co-morbidities. Structural changes have been found in frontal cortex and striatum in children and adolescents. A limited number of morphometric studies in Tourette syndrome persisting into adulthood suggest ongoing structural alterations affecting frontostriatal circuits. Using cortical thickness estimation and voxel-based analysis of T1- and diffusion-weighted structural magnetic resonance images, we examined 40 adults with Tourette syndrome in comparison with 40 age- and gender-matched healthy controls. Patients with Tourette syndrome showed relative grey matter volume reduction in orbitofrontal, anterior cingulate and ventrolateral prefrontal cortices bilaterally. Cortical thinning extended into the limbic mesial temporal lobe. The grey matter changes were modulated additionally by the presence of co-morbidities and symptom severity. Prefrontal cortical thickness reduction correlated negatively with tic severity, while volume increase in primary somatosensory cortex depended on the intensity of premonitory sensations. Orbitofrontal cortex volume changes were further associated with abnormal water diffusivity within grey matter. White matter analysis revealed changes in fibre coherence in patients with Tourette syndrome within anterior parts of the corpus callosum. The severity of motor tics and premonitory urges had an impact on the integrity of tracts corresponding to cortico-cortical and cortico-subcortical connections. Our results provide empirical support for a patho-aetiological model of Tourette syndrome based on developmental abnormalities, with perturbation of compensatory systems marking persistence of symptoms into adulthood. We interpret the symptom severity related grey matter volume increase in distinct functional brain areas as evidence of ongoing structural plasticity. The convergence of evidence from volume and water diffusivity imaging strengthens the validity of our findings and attests to the value of a novel multimodal combination of volume and cortical thickness estimations that provides unique and complementary information by exploiting their differential sensitivity to structural change.

Dataset Information

Brain mechanisms for prepulse inhibition in adults with Tourette syndrome: initial findings.

Publications

Brain mechanisms for prepulse inhibition in adults with Tourette syndrome: initial findings.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets