Neurobiological Studies of Functional Movement Disorders and Non-Epileptic Seizures
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 254
- Locations
- 2
- Primary Endpoint
- Genetics: S/S genotype of the serotonin transporter promoter region polymorphism.
Study Overview
Brief Summary
This study is part of a series of studies that will explore how the mind and the brain work to cause episodes of uncontrollable shaking in people who have no known underlying brain or medical disorder. The study is conducted at NIH and at the Brown University Rhode Island Hospital.
Healthy volunteers and people with functional movement disorders (FMD) or non-epileptic seizures (NES) who are 18 years of age or older may be eligible for this study.
Patients with NES have 3 teaspoons of blood drawn. The blood is tested for two genes that are normally found in healthy individuals to see if they are found more frequently in patients with uncontrolled shaking.
Patients with FMD have blood drawn for testing and also undergo functional magnetic resonance imaging (fMRI) to look at how the brain functions while the subject performs a specific task. MRI uses a strong magnetic field and radio waves to obtain images of body organs and tissues. During the scan, the subject lies on a table that can slide in and out of the scanner, a metal cylinder. The scan lasts about 60 to 90 minutes, during which the subject may be asked to lie still for up to 10 minutes at a time and to perform tasks, such as identifying the gender of faces shown on a screen.
Healthy volunteers may have blood drawn for genetic testing or fMRI or both.
Detailed Description
Objectives:
The study investigates the neurobiological correlates of conversion disorder (CD). The primary objectives are to investigate in CD patients:
- The role of emotional valence in an implicit emotional processing task (COMPLETE)
- The frequency of the 5HTTLPR S/S genotype
- Structural differences in grey matter of the brain as detected by voxel-based morphometry (VBM)
- The neural correlates of fear conditioning and fear extinction in a fear learning fMRI task
- The neural correlates of interoceptive activity in a Interoceptive Attention fMRI task
- Identifying the cortical physiology correlated with making a movement following a go command.
- Identifying the cortical physiology correlated with not making a movement following a no-go command.
- Identifying the cortical physiology correlated with planning to move or not move following a choose go-no go command.
Exploratory objectives are to investigate in CD patients:
- The frequency of several gene polymorphisms that are implicated in stress and affective disorder, including 5HTTLPR S/S (serotonin receptor), COMT (catechol-o-methyltransferase enzyme), Val/Met BDNF (brain-derived neurotrophic factor) and FKBP5 rs1360780 genotypes, as well as other polymorphisms or mutations to be determined later. Additionally, epigenetic data will be explored.
- The levels of salivary cortisol as a measure of stress.
- The heart rate variability, as a measure of autonomic nervous system function. (COMPLETE)
- Structural differences in white matter of the brain as detected by diffusion tensor imaging (DTI)
- The resting state BOLD fMRI signal
- The impact of the caregiver's attitude on the patients' symptoms
- The relationship between hemodynamic responses in regions implicated in interoception and self-reported measures of interoceptive attention, as well as behavioral and motor symptom severity
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 99 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •INCLUSION CRITERIA:
- •General Inclusion Criteria for FMD patients:
- •Diagnosis of clinically definite FMD utilizing Fahn and Williams criteria. The diagnosis must be made by a neurologist
- •Able to give informed consent
- •Age 18 or older
- •General Inclusion Criteria for Caregivers:
- •Age 18 or older
- •Able to give informed consent
- •Takes care of a patient with FMD patient enrolled in protocol 07-N-0190 for 10 or more weekly hours.
- •General Inclusion Criteria for PNES patients:
- •Diagnosis of PNES based on recording of patient s typical episode during 24 h video-EEG without concomitant EEG changes. The diagnosis must be made by a neurologist.
- •Able to give informed consent
- •Age 18 or older
- •General Inclusion Criteria for Healthy Volunteers:
- •Able to give informed consent
- •Age 18 or older
Exclusion Criteria
- •General exclusion criteria for FMD patients:
- •Significant neurological disorders (primary or comorbid) such as neurodegenerative disorders, stroke, movement disorders or epilepsy
- •Inflammatory disorders or autoimmune disorders active within the last 6 months
- •Patients with psychotic disorders or manic depression or active substance abuse within the last 6 months
- •Current suicidal ideation
- •Disease severity requiring inpatient treatment
- •Additional exclusion criteria for FMD patients for MRI:
- •Patients with movement symptoms at rest that may substantially inhibit resolution, comfort, or safety of MRI
- •Previous history of or MRI findings consistent with brain tumors, strokes, trauma or arterial venous malformations
- •History of traumatic brain injury with loss of consciousness or amnesia lasting greater than a few seconds
- •Contraindication to MRI
- •Pregnancy
- •Significant medical illness
- •Patients with current post-traumatic stress disorder
- •Patients on tricyclic antidepressants or antiepileptic medications 2 weeks prior to testing
- •General exclusion criteria for PNES patients:
- •Significant neurological disorders (primary or comorbid) such as neurodegenerative disorders, stroke, movement disorders or epilepsy
- •Inflammatory disorders or autoimmune disorders active within the last 6 months
- •Patients with psychotic disorders or active substance abuse within the last 6 months
- •Current suicidal ideation
- •Disease severity requiring inpatient treatment
- •General exclusion criteria for healthy volunteers:
- •Significant neurological disorders (primary or comorbid) such as neurodegenerative disorders, stroke, movement disorders or epilepsy
- •History of DSM IV-defined schizophrenia, schizoaffective disorder, bipolar disorder or major depression with psychosis
- •History of psychotic disorders or manic depression or active substance abuse within the last 6 months
- •Subjects with post-traumatic stress disorder
- •Subjects on antidepressants or antiepileptic medications
- •Inflammatory disorders or autoimmune disorders active within the last 6 months
- •Additional exclusion criteria for healthy volunteers for MRI:
- •Previous history of or MRI findings consistent with brain tumors, strokes, trauma or arterial venous malformations
- •Contraindication to MRI
- •Pregnancy
- •Significant medical illness
- •General Exclusion Criteria for Caregivers:
- •History of DSM-IV defined Schizophrenia, Schizoaffective Disorder, Bipolar Disorder, Major depression with psychotic features (by interview).
- •Active substance abuse within the past 6 months (by interview).
Arms & Interventions
fMRI study
subjects receiving MRI
Intervention: MRI (Device)
Outcomes
Primary Outcomes
Genetics: S/S genotype of the serotonin transporter promoter region polymorphism.
Time Frame: throughout
The S/S genotype of the 5HTTLPR polymorphism
fMRI study: blood oxygenation level dependent (BOLD) signal in the regions of interest during a gender identification task
Time Frame: throughout
fMRI BOLD signal change focusing on regions of interest during emotional valence task
Anatomical MRI: VBM
Time Frame: throughout
Structural grey matter brain data
Secondary Outcomes
No secondary outcomes reported