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.
