"Manual Dexterity and Oculomotor Control in Schizophrenia" (MADOCS)

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

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.

Study Overview

• Status: Unknown
• Conditions: Schizophrenia
• Intervention / Treatment: Device: Manual dexterity; Device: Oculomotor movements; Device: TMS coupled to EMG recording; Other: Psychopathological evaluations; Other: Neuropsychological evaluations

Detailed Description

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.

1. Control of manual dexterity will be assessed by a force sensor (Power Grip Manipulandum, PGM)
2. Oculomotor movements during behavioral task will be recorded using a video-oculography device
3. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 105
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marie GODARD; Phone Number: 00 33 1 45 65 77 28; Email: marie.godard@aphp.fr
• Study Contact Backup: Name: Isabelle Amado, Dr; Phone Number: 00 33 1 45 65 81 79; Email: i.amado@ch-sainte-anne.fr

Study Locations

• France
  • Paris, France, 75014
    • Recruiting
    • Centre de Recherche Clinique (CRC) - CHSA
    • Contact: Macarena CUENCA; Email: m.cuenca@ch-sainte-anne.fr
    • Contact: Cecile Bergot; Phone Number: 00 33 1 45 65 84 90; Email: c.bergot@ch-sainte-anne.fr
    • Principal Investigator: Macarena CUENCA
  • Paris, France, 75014
    • Not yet recruiting
    • Service Hospitalo-Universitaire (SHU) - CHSA
    • Contact: Marie GODARD; Phone Number: 00 33 1 45 65 77 28; Email: marie.godard@aphp.fr
    • Contact: Isabelle Amado; Phone Number: 00 33 1 45 65 81 79; Email: i.amado@ch-sainte-anne.fr
    • Principal Investigator: Isabelle Amado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All groups:

  1. 18>yrs<50
  2. Medical visit completed
  3. Visual acuity (9/10 for each eye or corrected)
  4. 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:

1. IQ<70,
2. 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.
3. Metallic implant in head (except dental fillings)
4. Pacemaker, or other electronic implanted devices
5. Central neurological disease: parkinsonism, x
6. Severe heart attack
7. Instable clinical state (e.g. stroke)
8. Previous history of drug abuse lasting more than 5 years or during the last year
9. Life event with a moderate to severe impact

10. Caffeine intake in the last two hours preceding visuomotor assessment

    • Groups of Siblings and Healthy controls:

11. No previous history of psychiatric disease, psychotic spectrum disorder (according to DIGS 3.0)

12. No previous history of antipsychotic medication (entire life)

    • Groups of UHR patient:

13. Chlorpromazine dose >100mg over more than 12 weeks
14. 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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier St Anne
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; University of Paris 5 - Rene Descartes
• Investigators: Study Director: Isabelle Amado, Dr, CHSA; Study Director: Pavel Lindberg, PhD, Institut National de la Santé Et de la Recherche Médicale, France

Publications and helpful links

General Publications

• Teremetz M, Amado I, Bendjemaa N, Krebs MO, Lindberg PG, Maier MA. Deficient grip force control in schizophrenia: behavioral and modeling evidence for altered motor inhibition and motor noise. PLoS One. 2014 Nov 4;9(11):e111853. doi: 10.1371/journal.pone.0111853. eCollection 2014.
• Amado I, Landgraf S, Bourdel MC, Leonardi S, Krebs MO. Predictive saccades are impaired in biological nonpsychotic siblings of schizophrenia patients. J Psychiatry Neurosci. 2008 Jan;33(1):17-22.

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2016
• Primary Completion (Anticipated): September 1, 2018
• Study Completion (Anticipated): January 1, 2019

Study Registration Dates

• First Submitted: May 20, 2016
• First Submitted That Met QC Criteria: July 5, 2016
• First Posted (Estimate): July 11, 2016

Study Record Updates

• Last Update Posted (Actual): October 19, 2017
• Last Update Submitted That Met QC Criteria: October 18, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Schizophrenia; Motor Control; TMS; Oculomotor; Sensorimotor Integration
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: D16-P01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO