[Show abstract][Hide abstract] ABSTRACT: Evidence suggests that Parkinson's disease (PD) patients produce large spatial errors when reaching to proprioceptively defined targets. Here, we examined whether these movement inaccuracies result mainly from impaired use of proprioceptive inputs for movement planning mechanisms or from on-line movement guidance. Medicated and non-medicated PD patients and healthy controls performed three-dimensional reaching movements in four sensorimotor conditions that increase proprioceptive processing requirements. We assessed the influence of these sensorimotor conditions on the final accuracy and initial kinematics of the movements. If the patterns of final errors are primarily determined by planning processes before the initiation of the movement, the initial kinematics of reaching movements should show similar trends and predict the pattern of final errors. Medicated and non-medicated PD patients showed a greater mean level of final 3D errors than healthy controls when proprioception was the sole source of information guiding the movement, but this difference reached significance only for medicated PD patients. However, the pattern of initial kinematics and final spatial errors were markedly different both between sensorimotor conditions and between groups. Furthermore, medicated and non-medicated PD patients were less efficient than healthy controls in compensating for their initial spatial errors (hand distance from target location at peak velocity) when aiming at proprioceptively defined compared to visually defined targets. Considered together, the results are consistent with a selective deficit in proprioceptively based movement guidance in PD. Furthermore, dopaminergic medication did not improve proprioceptively guided movements in PD patients, indicating that dopaminergic dysfunction within the basal ganglia is not solely responsible for these deficits.
Full-text · Article · Jun 2015 · Experimental Brain Research
[Show abstract][Hide abstract] ABSTRACT: Introduction and Objectives:
Tic disorders, like Tourette Syndrome, are neurodevelopmental conditions afflicting up to 3%1 of children worldwide. Moreover, about 50%2 of patients will continue to experience symptoms through adulthood, hence lowering their quality of life and increasing the social stigma. In both children and adults, tic disorders’ evaluation and treatment are still hindered by the large amount of conflicting neurobiological data. In fact, motor functions and cognitive processes (especially inhibition and memory) might be strongly affected in tic patients. The inclusion of patients presenting distinct phenotypes might explain this large heterogeneity in studies. Four main phenotypes were identified by factor analyses3 : i) tics with attention deficit disorder, ii) tics with obsessive-compulsive disorder, iii) simple tics (eg. eye twitches), and iv) complex tics (eg. knee jerks). Several studies have shown functional brain differences between patients from the first two groups. However, very few have investigated the possible brain dissimilarities between patients predominantly exhibiting simple versus complex tics. Hence, we aimed to evaluate the impact of tic complexity on cognitive processes, more precisely inhibition and memory’s context updating, using Event-Related Potentials (ERP) techniques.
ERPs were recorded and compared (MANOVAs) in 12 patients exhibiting simple tics, 12 patients showing complex tics and a control group of 15 healthy adults matched to patients on age, sex and intelligence. Tic complexity was assessed using the YGTSS. To measure inhibition (N200) and context updating (P300) processes, participants completed two classical oddball tasks. Tasks were identical, except for the type of response, in order to further investigate the role of cognitive load on inhibition and memory. The motor task required participants to press different buttons when they perceived frequent (“O”) and rare (“X”) stimuli (ie. with 80% and 20% probabilities of occurrence, respectively). In the non-motor task, participants had to mentally count the number of rare stimuli.
Results and Discussion:
Both groups of tic patients showed an enhanced N200 in the frontal region during the non-motor task (F(2,36) = 5.7, p<.01). This increase was correlated with tics severity (r= .42, p<.05), suggesting that patients might have developed compensatory neural mechanisms to overcome inhibition deficits. Regarding the P300, patients with simple tics showed the most reduced amplitude during the non-motor task, while patients exhibiting complex tics showed the largest reduction during the motor task (F(2,36) = 3.4, p<.05). P300 amplitude reductions were correlated with tic intensity (r= .54; p<.01), suggesting that neural activity dedicated to tics might interfere with memory’s context updating processes.
Our results suggest that tic complexity and tasks’ cognitive load can modulate tic patients' neural mechanisms. Conflicting results found in previous studies with children and adults might have been confounded by these variables. Our study underlines the impact of clinical symptoms on cognitive assessment.
1. Knight T. et al., Prevalence of tic disorders: a systematic review and meta-analysis, Pediatr Neurol. 47:77-90, 2012
2. Leckman JF. et al., Course of tic severity in Tourette syndrome: the first two decades, Pediatrics. 102:14-19, 1998
3. Grados MA. et al., Clinical phenomenology and phenotype variability in Tourette syndrome, J Psychosom Res. 67:491-496, 2009
Disclosures: The authors report no conflict of interest.
[Show abstract][Hide abstract] ABSTRACT: Background:
Tic disorders, such as the Gilles de la Tourette syndrome and persistent tic disorder, are neurodevelopmental movement disorders involving impaired motor control. Hence, patients show repetitive unwanted muscular contractions in one or more parts of the body. A cognitive-behavioral therapy, with a particular emphasis on the psychophysiology of tic expression and sensorimotor activation, can reduce the frequency and intensity of tics. However, its impact on motor activation and inhibition is not fully understood.
To study the effects of a cognitive-behavioral therapy on electrocortical activation, we recorded the event-related potentials (ERP) and lateralized readiness potentials (LRP), before and after treatment, of 20 patients with tic disorders and 20 healthy control participants (matched on age, sex and intelligence), during a stimulus-response compatibility inhibition task. The cognitive-behavioral therapy included informational, awareness training, relaxation, muscle discrimination, cognitive restructuration and relapse prevention strategies.
Our results revealed that prior to treatment; tic patients had delayed stimulus-locked LRP onset latency, larger response-locked LRP peak amplitude, and a frontal overactivation during stimulus inhibition processing. Both stimulus-locked LRP onset latency and response-locked LRP peak amplitude normalized after the cognitive behavioral therapy completion. However, the frontal overactivation related to inhibition remained unchanged following therapy.
Our results showed that P300 and reaction times are sensitive to stimulus-response compatibility, but are not related to tic symptoms. Secondly, overactivity of the frontal LPC and impulsivity in TD patients were not affected by treatment. Finally, CBT had normalizing effects on the activation of the pre-motor and motor cortex in TD patients. These results imply specific modifications of motor processes following therapy, while inhibition processes remained unchanged. Given that LRPs are partially generated within the sensorimotor and supplementary motor area, the reported reduction in tic frequency and improvements of LRPs components suggest that CBT induced a physiological change in patients' motor area.
No preview · Article · May 2015 · Neuropsychologia
[Show abstract][Hide abstract] ABSTRACT: Introduction: Tourette syndrome (TS) is a neuropsychiatric disorder involving motor and phonic tics. Studies have shown that a therapy based on regulating the chronically heightened sensorimotor activation and elevated muscle tension could improve motor performance and general condition in TS patients. Still, physiological and behavioural mechanisms behind the therapy are not fully understood.
Objectives: This project aims to study the activation and inhibition of motor processes in TS patients, and the psychophysiological modifications induced by the therapy.
Method: Twenty participants with motor tics were matched on age, sex and intelligence with 20 healthy controls. EEG activity was recorded at 500 Hz, at electrodes C3 and C4, during a Stimulus-Response Compatibility task. EEG data was averaged into stimulus-locked event-related potentials. Lateralized readiness potentials (LRP) were then obtained through a double subtraction, to eliminate any electrical activity unrelated to motor processes. Measures were taken before and after the therapy for the TS group, while the control group was only tested once.
Results: Before the therapy, the LRP onset was significantly slower for TS patients, compared to controls [F(1,38)=4.243, p<0.05]. After the therapy, this difference disappeared. In the TS group, the LRP onset was significantly faster after the therapy [F(1,19)=7.782, p<0.05].
Conclusion: The group difference on the LRP onset latency disappears after the therapy, suggesting that the therapy induces a normalization of pre-motor processes. It could lead TS patients to have a greater control of movement preparation. These results could also indicate a modification of the cerebral activity in the supplementary motor area.
[Show abstract][Hide abstract] ABSTRACT: Introduction: Tourette Syndrome (TS) is a neuropsychiatric disorder characterized by both multiple motor tics and at least one phonic tic. Chronic tic disorder (CTD) is characterized by either motor or vocal tics, but not both. These two conditions are part of the "tic disorders" category in the DSM. However, the distinction between these two conditions is only based on tic symptoms, and not on a neurophysiological basis. The need for a distinction has been debated, since phonic tics have an inherent motor component.
Aims: This project aims to evaluate the event-related potentials (ERP) in TS and CTD patients, to find similarities or differences between the two groups.
Methodology: Eleven patients with TS have been paired on age, sex and intelligence with 11 patients with CTD and 11 healthy participants. Electroencephalographic (EEG) data was recorded in a stimulus-response compatibility paradigm (SRC), and averaged stimulus-locked. The ERP component used in this experiment is the late positive component (LPC). The LPC has been measured as the maximum peak in a 400-800 ms time window.
Results: The analysis revealed a trend toward a group difference on the LPC [F(2,30) = 2.942, p = .06], for the incompatible condition, in the parietal region. A post-hoc analysis (Tukey) revealed a significant difference between TS patients and controls (p = .05), but there was no significant difference between TS patients and CTD patients, nor between CTD patients and controls.
Conclusion: Based on these results, it seems that there's no neurophysiological difference between TS and CTD. Indeed, both groups present the same parietal overactivation during stimulus-response incompatibility. TS and CTD patients might need to maintain a high level of activation to process this conflictual situation.
Limits: A higher number of participants could reduce the size of the standard deviations, which were really high and limited the significance of results.
[Show abstract][Hide abstract] ABSTRACT: The aim of this review is to assess new, emerging, and experimental treatment options for tardive dyskinesia (TD). The methods to obtain relevant studies for review included a MEDLINE search and a review of studies in English, along with checking reference lists of articles. The leading explanatory models of TD development include dopamine receptor supersensitivity, GABA depletion, cholinergic deficiency, neurotoxicity, oxidative stress, changes in synaptic plasticity, and defective neuroadaptive signaling. As such, a wide range of treatment options are available. To provide a complete summary of choices we review atypical antipsychotics along with resveratrol, botulinum toxin, Ginkgo biloba, tetrabenazine, clonazepam, melatonin, essential fatty acids, zonisamide, levetiracetam, branched-chain amino acids, drug combinations, and invasive surgical treatments. There is currently no US Food and Drug Administration-approved treatment for TD; however, prudent use of atypical antipsychotics with routine monitoring remain the cornerstone of therapy, with experimental treatment options available for further management.
Full-text · Article · Nov 2013 · Drug Design, Development and Therapy
[Show abstract][Hide abstract] ABSTRACT: Parkinsonism (or Parkinson's syndrome [PS]) remains common in patients exposed to antipsychotic drugs. One clinical tool used in its detection and follow-up, the Simpson-Angus Scale (SAS), has been under revision lately. We further examined the discriminative power of the SAS to detect PS and its efficacy as a measure of PS intensity in chronic schizophrenia.
Fifty-six outpatients between 50 and 75 years of age, under stable antipsychotic drug therapy, provided consent to undergo an evaluation along the SAS and Unified Parkinson's Disease Rating Scale III motor subsection, split according to the presence or absence of PS defined in the UK Parkinson's Disease Society Brain Bank (UKPDSBB) criteria or Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria.
The identification rate for PS was 39.3% based on UKPDSBB criteria applied to the Unified Parkinson's Disease Rating Scale III, compared with 62.5% and 87.5% according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and SAS cutoff value greater than 0.3, respectively. Median SAS scores for PS and PS-free participants were comparable. The SAS yielded high sensitivity (90.9%) but low specificity (17.7%). κ Values generally revealed only slight agreement between the group allocation provided by the SAS and the UKPDSBB criteria. Receiver operating characteristic curve for screening performance of the SAS provided poor prediction of subject status.
The SAS lacks specificity and constitutes an imperfect detection and measurement tool for PS in older adults. Raising the cutoff score would avoid inflation in PS identification. The scale is probably best used as a measure of change relative to baseline score following an intervention, but results should be interpreted with caution.
No preview · Article · Oct 2013 · Journal of clinical psychopharmacology