Manual Dexterity and Oculomotor Control in Schizophrenia

Study Overview
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Brief Summary
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The investigators recently showed that visuomotor integration was significantly altered in schizophrenic patients during: (i) a grip force task (Teremetz et al., 2014), and (ii) a saccadic paradigm (oculomotor task)(Amado et al., 2008). Given this findings, the investigators propose a combined study of oculomotor and grip force control to better characterize the sensorimotor integration deficit. This approach may allow for identification of behavioural biomarkers of vulnerability to develop schizophrenia.

Detailed Description
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1 - Scientific background and rational Use of sensory cues is essential for execution and correction of voluntary movements. The motor areas and their regulation is of special interest in patients with schizophrenia as there is clear evidence of motor abnormalities independent of the effects of antipsychotic medication, even before the onset of the disorder. Sensorimotor abnormalities have been proposed as a valid endophenotype in schizophrenia. Our global objective is to study and provide vulnerability markers for schizophrenia. Control of manual dexterity will be assessed by a force sensor (Power Grip Manipulandum, PGM) Oculomotor movements during behavioral task will be recorded using a video-oculography device The involvement of cortical inhibition in this volitional inhibition task will be studied by neuronavigation guided TMS coupled to EMG recording 2 - Description of the project methodology There is strong evidence for schizophrenia being a neuro-developmental disorder (Rapoport et al., 2005). It has been shown, for many years, that patients with schizophrenia exhibit abnormal patterns of sensorimotor integration (Manschreck et al., 1982), which is the capacity to integrate different sensory stimuli into appropriate motor actions. It is clinically relevant, in terms of early diagnosis and prevention, whether deficient sensorimotor integration is present in the prodromal phase of schizophrenia, and whether this constitutes a vulnerability marker for the disease. Our global objective is to study the interactions and related substratum of oculomotor movements during force control task. The secondary objectives: (i) To show that increased motor noise is indeed present in schizophrenia. (ii) To show by TMS that cortical excitability in the primary motor cortex (M1) is task-modulated and decreased in schizophrenia. (iii) Assess the role of deficient cortical inhibition in these behavioral deficits To this end, three different groups of subjects will be studied: schizophrenic patients, non-affected siblings, ultra high risk patients, non-treated schizophrenic patients and healthy control subjects.

Official Title
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MADOCS: Manual Dexterity and Oculomotor Control as Vulnerability Markers in Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Device: Manual dexterity
* Device: Oculomotor movements
* Device: TMS coupled to EMG recording
* Other: Psychopathological evaluations
* Other: Neuropsychological evaluations


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All groups: 18>yrs<50 Medical visit completed Visual acuity (9/10 for each eye or corrected) Provided written informed consent Group of patient suffering from schizophrenia: 4. DSM-IV-TR diagnostic criteria for schizophrenia 5. Treatment: stable atypical anti-psychotic medication for >3 months prior to the study Group of UHR patient: 6. 18>yrs<30 7. Fulfill at risk criteria of CAARMS diagnostic tool Exclusion Criteria: • All groups: IQ<70, Contraindications for TMS protocol: no previous history of neurosurgery or seizures or 1st degree relative with history of seizures, heart disease, drug abuse or addiction in the last 12 months, medications that lower seizure threshold including clozapine, bupropion, méthadone or theophylline. Metallic implant in head (except dental fillings) Pacemaker, or other electronic implanted devices Central neurological disease: parkinsonism, x Severe heart attack Instable clinical state (e.g. stroke) Previous history of drug abuse lasting more than 5 years or during the last year Life event with a moderate to severe impact Caffeine intake in the last two hours preceding visuomotor assessment • Groups of Siblings and Healthy controls: No previous history of psychiatric disease, psychotic spectrum disorder (according to DIGS 3.0) No previous history of antipsychotic medication (entire life) • Groups of UHR patient: Chlorpromazine dose >100mg over more than 12 weeks No previous history of autism spectrum disorder, bipolar disorder or diagnozed schizophrenia (according to DSM-IV-TR criteria), isolated anxiety disorders (e.g. social phobia, agoraphobia)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Schizophrenia<br>40 patients with diagnosis of schizophrenia (25 medicated - 15 non-medicated) | Device: Manual dexterity<br>* Control of manual dexterity will be assessed by a force sensor (Power Grip Manipulandum, PGM)<br>Device: Oculomotor movements<br>* Oculomotor movements during behavioral task will be recorded using a video-oculography device<br>Device: TMS coupled to EMG recording<br>* The involvement of cortical inhibition in this volitional inhibition task will be studied by neuronavigation guided TMS coupled to EMG recording<br>Other: Psychopathological evaluations<br> <br> Other: Neuropsychological evaluations<br> <br> |
| Other: Healthy sibling<br>25 healthy siblings | Device: Manual dexterity<br>* Control of manual dexterity will be assessed by a force sensor (Power Grip Manipulandum, PGM)<br>Device: Oculomotor movements<br>* Oculomotor movements during behavioral task will be recorded using a video-oculography device<br>Device: TMS coupled to EMG recording<br>* The involvement of cortical inhibition in this volitional inhibition task will be studied by neuronavigation guided TMS coupled to EMG recording<br>Other: Psychopathological evaluations<br> <br> Other: Neuropsychological evaluations<br> <br> |
| Other: Ultra high risk for developing Schizophrenia<br>15 patients with ultra high risk for developing Schizophrenia | Device: Manual dexterity<br>* Control of manual dexterity will be assessed by a force sensor (Power Grip Manipulandum, PGM)<br>Device: Oculomotor movements<br>* Oculomotor movements during behavioral task will be recorded using a video-oculography device<br>Device: TMS coupled to EMG recording<br>* The involvement of cortical inhibition in this volitional inhibition task will be studied by neuronavigation guided TMS coupled to EMG recording<br>Other: Psychopathological evaluations<br> <br> Other: Neuropsychological evaluations<br> <br> |
| Other: Controls<br>-25 age and gender-matched healthy controls | Device: Manual dexterity<br>* Control of manual dexterity will be assessed by a force sensor (Power Grip Manipulandum, PGM)<br>Device: Oculomotor movements<br>* Oculomotor movements during behavioral task will be recorded using a video-oculography device<br>Device: TMS coupled to EMG recording<br>* The involvement of cortical inhibition in this volitional inhibition task will be studied by neuronavigation guided TMS coupled to EMG recording<br>Other: Psychopathological evaluations<br> <br> Other: Neuropsychological evaluations<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Behavioural assessment | Index reflecting motor performance during visuomotor task (including force and oculomotor control) | BASELINE | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical scale : PANSS | Positive and Negative Syndrome Scale: Assess positive and negative symptoms | BASELINE | 
| Clinical scale : DIGS III | Diagnostic Interview for Genetic Studies 3.0: Overview of clinical state | BASELINE | 
| Clinical scale : BPRS | Brief Psychiatric Rating Scale: Assess schizophrenic symptoms | BASELINE | 
| Clinical scale : SAS | Simpson Angus Extra-Pyramidal Scale: Asses extra-pyramidal signs | BASELINE | 
| Clinical scale : AIMS | Abnormal Involuntary Movements Scale: Assess abnormal involuntary movements | BASELINE | 
| Clinical scale : TAP | Test battery for Attentional Performance: Assess attentional capacity (e.g. working memory) | BASELINE | 
| Clinical scale : Stroop | Stroop color naming test: Assess selective attention or inhibition. | BASELINE | 
| Clinical scale : WASI | Wechsler Abbreviated Scale of Intelligence: Assess intelligence quotient | BASELINE | 
| Tracking performance (motor task): RMS Error | RMS Error (Root Mean Square) | BASELINE | 
| Tracking performance (motor task): Coefficient of variability | Coefficient of variability | BASELINE | 
| Tracking performance (motor task): Timing | Timing/inhibition | BASELINE | 
| Ocolomotor performance (eye tracker) : Saccade | Saccade error (back up/ catch up saccades) during smooth pursuit and fixation | BASELINE | 
| Ocolomotor performance (eye tracker): Gain | Gain (target velocity/gaze velocity), Reaction time | BASELINE | 
| Ocolomotor performance (eye tracker): Amplitude of eye movements | Amplitude (°) and velocity (°/s) of saccadic movements | BASELINE | 
| Motor noise | Variability of EMG response during visuomotor task | BASELINE | 
| Cortical excitability (MEP; TMS) | Motor evoked potential (MEP) during visuomotor task (single pulse TMS) | BASELINE | 
| Cortical inhibition (SICI; TMS) | Cortical inhibition measured during visuomotor task (paired-pulse TMS; MEP) | BASELINE | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sensorimotor Integration, Schizophrenia, TMS, Oculomotor, Motor Control