Neurobiology of Functional Movement Disorder and Non-Epileptic Seizures
Mots clés
Abstrait
La 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 population:
We intend to study adult patients with diagnoses of functional movement disorders (FMD) seen by the Human Motor Control Section clinic (HMCS), patients with diagnoses of psychogenic non-epileptic seizures (PNES) seen by the Epilepsy clinic and healthy volunteers. Up to 12 healthy volunteers will be for the EEG-EMG sub-study. The PNES patient group will include patients seen at Rhode Island Hospital. Additionally, we would like to study caregivers of patient's with FMD who are enrolled un protocol 07-N-0190.
Design:
An assessment for psychiatric diagnoses and measurement scales will be administered to the FMD and PNES patients, healthy volunteer controls and caregivers.
- Functional MRI (fMRI): emotional processing will be studied using a gender identification task with differing emotional valences. (COMPLETE) Limbic processing will also be studied using a fear learning fMRI task. Resting state BOLD fMRI signal will also be obtained.
- Anatomical MRI: VBM and DTI will be performed using anatomical MRI sequences collected during the fMRI scanning or subsequent dedicated anatomical MRI sessions.
- Genetics: blood will be collected for testing.
- Stress biomarkers: saliva will be collected for testing. [EVALUATION IN HEALTHY VOLUNTEERS COMPLETE].
- Autonomic nervous system function: electrocardiogram (EKG) will be obtained to determine heart rate variability. [COMPLETE].
- Event related potentials: 64-channel EEG and surface EMG will be recorded during a go , no-go and choose go-no go behavioral task.
- EEG will be recorded during the resting state condition (five minutes with eyes open and five minutes with eyes closed).
Outcome measures:
- fMRI study: blood oxygenation level dependent (BOLD) signal in the regions of interest during a gender identification task (primary) [COMPLETE], in regions of interest during a fear learning task (primary), as well as resting state BOLD signal (exploratory). EEG resting state data will be compared and correlated with the fMRI resting state data.
- Anatomical MRI: VBM (primary) and DTI (exploratory)
- Genetics: (a) S/S genotype of the serotonin transporter promoter region polymorphism. (primary) (b) Polymorphism frequency of several genes related to affective disorders and/or stress (exploratory)
- Stress biomarkers: salivary cortisol levels (exploratory). [EVALUATION IN HEALTHY VOLUNTEERS COMPLETE]
- Autonomic nervous system function: heart rate variability as measured by EKG (exploratory). [COMPLETE]
- Psychological profile scales: scores exploratory.
- The relationship between hemodynamic responses in regions implicated in interoception and self-reported measures of IA, motor symptoms and behavioral ratings (exploratory)
- EEG-EMG study: Characteristics of event related cortical potentials correlated with simple behavioral motor tasks in healthy volunteers. Differences between go and no-go potentials will be identified and quantified. This analysis will allow planning a properly powered study for patients with functional movement disorders.
Rendez-vous
| Dernière vérification: | 10/26/2020 |
| Première soumission: | 07/11/2007 |
| Inscription estimée soumise: | 07/11/2007 |
| Première publication: | 07/12/2007 |
| Dernière mise à jour soumise: | 11/10/2020 |
| Dernière mise à jour publiée: | 11/12/2020 |
| Date de début réelle de l'étude: | 10/04/2007 |
| Date d'achèvement primaire estimée: | 12/30/2021 |
| Date estimée d'achèvement de l'étude: | 12/30/2021 |
Condition ou maladie
Intervention / traitement
Device: fMRI study
Phase
Groupes d'armes
| Bras | Intervention / traitement |
|---|---|
| Experimental: fMRI study subjects receiving MRI | Device: fMRI study The imaging study will use a block design to (i) optimize amygdala activation to emotionally balanced images, (ii) to optimize analysis of PPI and (iii) to optimize the go/notask design. G. T2- sensitive functional images will be obtained on a MRI system with a 1.5 Tesla superconducting magnet and a standard head coil. An echo planar image sequence (TR=2500msec, TE=33 msec, 90 flip angle) with 30 contiguous 2mm thick coronal oblique slices with 1 mm interslice gap centered over the amygdala, tilted 30 to the anterior, to improve susceptibility artifact. Three dimensional anatomical images will be taken for the co-registration of the functional images. |
Critère d'éligibilité
| Âges éligibles aux études | 18 Years À 18 Years |
| Sexes éligibles à l'étude | All |
| Méthode d'échantillonnage | Non-Probability Sample |
| Accepte les bénévoles en santé | Oui |
| Critères | - 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). |
Résultat
Mesures des résultats primaires
1. fMRI study: blood oxygenation level dependent (BOLD) signal in the regions of interest during a gender identification task [throughout]
2. Genetics: S/S genotype of the serotonin transporter promoter region polymorphism. [throughout]
3. Anatomical MRI: VBM [throughout]
